Cytokines are the hormonal messengers responsible for most of the biological effects in the immune system, such as cell-mediated immunity and allergic type responses. T lymphocytes are a major source of cytokines. These cells bear antigen-specific receptors on their cell surface to allow recognition of foreign pathogens. There are two main subsets of T lymphocytes, distinguished by the presence of cell surface molecules known as CD4 and CD8. T lymphocytes expressing CD4 are also known as helper T cells, and these are regarded as being the most prolific cytokine producers. This subset can be further subdivided into Th1 and Th2, and the cytokines they produce are known as Th1-type cytokines and Th2-type cytokines.
- Th1 cells Type 1 helper T cells are characterized by the production of pro-inflammatory cytokines like IFN-γ, IL-2, and TNF-β. Th1 cells are involved in cell-mediated immunity. The cytokines produced by Th1 cells stimulate the phagocytosis and destruction of microbial pathogens. Several chronic inflammatory diseases have been described as Th1 dominant diseases i.e. multiple sclerosis, diabetes, and rheumatoid arthritis.
- Th2 cells Type 2 helper T cells are characterized by the production of IL-4, IL-5, IL-9, IL-10, and IL-13. Th2 cells are thought to play a role in allergy responses. Cytokines like IL-4 generally stimulate the production of antibodies directed toward large extracellular parasites. IL-5 stimulates eosinophil responses, also part of the immune response toward large extracellular parasites. Atrophy and allergy are thought to be Th2 dominant conditions.
Improved understanding of Th1 and Th2 differentiation will improve our overall understanding of the immune system, its response to infection and aberrant responses that lead to disease.
The immune balance controlled by T helper 1 (Th1) and T helper 2 (Th2) is crucial for immunoregulation and its imbalance causes various immune diseases including allergic asthma. Therefore, diagnosis of Th1/Th2 balance in autoimmune diseases including asthma is essential for the application of immune balance regulating drugs. Th1/Th2 balance is not only controlled by Th1 cells and Th2 cells, but also by various regulatory factors including regulatory T cells, sexual factor, chemokines, transcription factors, signal transduction pathway (STAT6) etc. Current research strategies seek to exploit these observations to improve the generation of novel targets for regulating Th1/Th2 balance. The Th1/Th2 balance could be influenced by imunomodulatory drugs (including herbs, prescription and its main components) but this way of therapy needs further evaluation focused on this various factors and synergistic effect.
Both naturally occurring and inducible CD4+CD25+ regulatory T cells inhibit these inappropriate immune responses in Th1/Th2 balance. Sexual hormones especially testosterone promotes IFN-γ production from CD4 cells isolated from multiple sclerosis patients and estradiol promotes IL-4 cytokines in spleen cells of C57BL/6 mice. Chemokines, including thymus and activation-regulated chemokine (TARC), are responsible for trafficking of Th2 lymphocytes into sites of allergic inflammation, that depended on regulation by the STAT6 (signal transducers and activators of transcription 6)-mediated pathways and increases in TARC promote Th2 trafficking. T-box expressed in T cells (T-bet) is thought to initiate Th1 development while inhibiting Th2 cell differentiation. GATA-binding protein 3 (GATA-3) plays a pivotal role in the development of the Th2 phenotype while inhibiting Th1 cells.
The principal role of the immune system is thought to be host defense against invasion by pathogenic agents. For this reason, the study of the immunology of infection offers important insight concerning effector functions and regulatory interactions fundamental to the immune response. In reacting to infectious agents, the immune system can generate to varying degrees unwanted immunopathologic side effects in the form of fever, tissue damage and immune complex lesions. The balance between resistance and pathology is delicate and determined both by the virulence of the pathogen and the immunoregulatory state of the host. It has become increasingly clear that cytokines, and in particular those associated with the Th1/Th2 CD4+ T cell subsets, are key determinants of the beneficial vs disease consequence of the host response.
When Th1 cells produce IFN-γ, this prompts the macrophages to produce TNF and toxic forms of oxygen which destroy the microorganisms within the phagosomes and lysosomes. On the other hand, when Th2 cells produce IL-4 and IL-10, these cytokines block the microbe killing that is activated by IFN-γ.
The Th1/Th2 relationship has also been investigated in regards to transplantation. Th1 responses have been implicated in most forms of acute rejection and graft versus host disease, while Th2 responses have been variably associated with either protection or chronic rejection. However, cloned Th1 or Th2 cells have a similar capacity to reject skin grafts in experimental models, and regulatory T lymphocytes (Tr1/Treg cells) are now being implicated in protection and tolerance induction. The fetus is also analogous to an allograft and Th2 or Treg responses are thought to be protective, while Th1 responses may lead to resorption or spontaneous abortion.
Immune system, composed of Th1-mediated cellular (Type 1) immunity and Th2-mediated humoral (Type 2) immunity, is essential to maintain our health. Both Type 1 and Type 2 immunity is tightly controlled because excessive activation may cause various immune diseases such as diabetes and liver injury by Type1, and allergy and tumor genesis by Type 2. Therefore, the regulation of the ‘immune balance’ between Type 1 and Type 2 immunity is critical for prevention and therapy of the immune diseases.
Common Th1 dominance disorders
Organ-specific autoimmune diseases
Multiple sclerosis IBD/Crohn’s disease Type 1 diabetes Hashimoto’s disease, Graves disease (thyroiditis) Psoriasis Rheumatoid arthritis Heliobacter pylori induced peptic ulcer
Common Th2 dominance disorders
Systemic autoimmune diseases
Allergies Asthma Chronic sinusitis Many cancers Hepatitis B and C (mixed Th1 and Th2) Ulcerative colitis Viral infections Systemic lupus erythematosus Helminth infections
Autoimmune disease: An immune system out of balance
Virtually all autoimmune diseases -– conditions where the immune system begins to attack self-tissue –- have either a Th1 or a Th2 dominance. Put another way, autoimmune conditions generally have either a T cell upregulation and B cell suppression (Th1 dominant) or the opposite (Th2 dominant).
|Th1 dominant: T cells up; B cells down||Th2 dominant: T cells down; B cells up|
It’s imperative that people with autoimmune disorders maintain Th1/Th2 balance. When the immune system is dysregulated and starts attacking body tissues, the more out of balance the immune system is, the more voraciously it will attack those tissues. For example, in someone with rheumatoid arthritis, an autoimmune condition where the immune system attacks cartilage, the more out of balance the Th1/Th2 system is, the more cartilage destruction will take place.
Regulatory T cells diversity & Th1/Th2 balance
‘Naturally occurring’ CD4+ T regulatory cells (nTreg) are derived centrally in the thymus and constitutively express CD25 (the α chain of the IL-2 receptor) and other suppressive molecules including CTLA-4 (1, 2). These cells generally appear to exert suppressive effects by direct cell contact rather than cytokine production. The Foxp3 (forkhead box P3) gene appears to be a critical regulator of the development of this subgroup of CD4+CD25+ Trn cells. At a population level, there has been a parallel rise in both Th1-mediated autoimmune diseases (such as type 1 diabetes, inflammatory bowel disease, multiple sclerosis) and Th2-mediated allergic diseases.
At the individual level, there is accumulating evidence that atopy is associated with an increase in both Th1 and Th2 responses. Furthermore, Th1 cells also appear to play a role in allergic inflammation in local tissues, failing to counter balance Th2 responses in airways inflammation.
These observations lead to the opinion that the autoimmune diseases may develop as a result of a more fundamental failure of underlying immune regulation, rather than a simple skewing of immune response along a Th1/Th2 homeostasis as previously thought
The regulation of normal and allergic immune responses to allergens in the mucosa is still poorly understood, and the mechanism of specific immunotherapy in normalizing the allergic response to such allergens is currently not clear. Numerous studies have demonstrated alterations in T cell reactivity after allergen immunotherapy, with reduction in Th2 cytokine expression upon allergen stimulation often accompanied by increased expression of the Th1-associated cytokine IFN-γ (8, 9). Recently, attention has focused on IL-10, an immunodulatory cytokine that can down regulate production of both Th1 and Th2 cytokines. Several groups have suggested that allergen immunotherapy induces a CD25+ IL-10- producing regulatory T cell subset .
Cytokines are of major importance because IL-4 and IL-13 induce the production of IgE by B cells and IL-5 regulates the growth, differentiation, and activation of eosinophil. Both IL-4 and IL-5 can directly induce AHR (airway hyperreactivity), airway and blood eosinophilia in asthmatic patients. The role of Th1-type cytokine IFN-γ in asthma is still a matter of debate: in an earlier study Krug and coworkers described an increased frequency of IFN-γ + T cells in bronchoalveolar lavage fluid from asthmatic compared with control subject, and Hessel and colleagues have early demonstrated that the development of AHR is IFN-γ dependent. However, other investigators have shown an inhibitory effect of IFN-γ on pulmonary allergic responses.
nTreg cells constitutively express cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), whereas other types of T cells express it after activation. It has been shown that blockade of CTLA-4 in vitro inhibits nTreg cell–mediated suppression. Foxp3 is believed to be a master regulator of CD25+ Treg cell development and function. A transcription factor specific for naturally occurring Treg cells is Foxp3, a forkhead box transcription factor that is involved in the induction of the suppressor phenotype of these cells.
These cells can also function through induction of inhibitory cytokines, such as transforming growth factor-β (TGF-β. IL-10 was originally described as a cytokine produced by Th2 cells. However, it soon became clear that this suppressive cytokine was produced by other cells, including Th1 cells.
Sexual factors & Th1/Th2 balance
Many autoimmune diseases preferentially affect women. The underlying reasons for this gender bias are not clear, but are thought to relate to the effects of sex hormones on the immune system. Males and females appear to show differential responses in many immunological settings. Females were shown to have a more developed thymus, greater resistance to tolerance induction in some animal models, and more pronounced tumor allograft rejection. Women have elevated immunoglobulin levels compared to men and an elevated CD4/CD8 T cell ratio in peripheral blood. Conversely, women compared to men show a reduced antibodydependent cell-mediated and natural killer (NK) cell cytotoxicity
The heightened immune responsiveness in females may contribute to the greater susceptibility of women to autoimmune diseases such as asthma, multiple sclerosis (MS), rheumatoid arthritis (RA), Grave’s disease, systemic lupus erythematosus (SLE), myasthenia gravis, Sjogren’s syndrome, and Hashimoto’s thyroiditis.
Very few studies of sex differences involving cytokine production in vivo have been reported to date. Nevertheless, sex steroids seem to differentially affect Th1 and Th2 cytokine production. Sex steroid hormones are produced by the ovaries and the testes and include estrogens, progestins, and androgens (such as testosterone). Steroid hormones, such as cortisol or dihydoepiandrosterone (DHEA) are produced by the adrenal gland. Protein hormones, such as prolactin, are produced by in the anterior pituitary. Binding sites for sex steroids are present on lymphocytes and they can be metabolized in immunocompetent cells, suggesting that sex steroids may affect leukocyte function directly.
Estrogen has effects beyond modulation of sex differentiation, sex function, and its effects on immune cells. Estrogen was shown to directly influence cytokine secretion by CD4 T-cell clones isolated from multiple sclerosis patients. Although some studies show contradictory findings, the large majority of literature suggests that androgens and progesterone have immunosuppressive effects, prolactin is stimulatory, and estrogen can be either stimulatory (at low doses) or inhibitory (at higher doses) for immune function
Studies suggest that high levels of 17β-estradiol present during days 14–18 of the menstrual cycle down-regulate the CD3+CD8+cytolytic T cell activity in the uterus. In contrast to most findings, a recent human study showing the in vivo effects of sex steroids on lymphocyte responsiveness demonstrated that women treated with androgens showed significantly enhanced mitogen-induced IFN-γ/IL-4 ratios and increased TNF-α production. Studies of pregnancy have suggested that sex steroids may drive the balance toward Th1 or Th2 cytokine responses. Whitacre et al. (39) propose that females are more likely than males to develop a Th1 profile when challenged with an infectious agent. Hamano et al. showed that estrogen levels similar to those during pregnancy can stimulate production of the Th2 cytokine, IL-4, from human PBMC (peripheral blood mononuclear cells).
Huber et al. showed that testosterone promotes IFN-γ production from CD4 cells and estradiol promotes IL-4 cytokines in spleen cells of C57BL/6 mice. Nevertheless, there is considerable uncertainty about how sex hormones regulate cytokine release and the Th1/Th2 balance. More must be learned about estrogen-regulated genes and the effect of estrogen therapy on promoters for Th1 and Th2 cytokines.
The cross-regulatory nature of the Th1/Th2 balance suggests that maturing lymphocytes can change their secretory pattern over time and specific sex steroids may produce different modulatory effects depending on the cytokine profile of the cells at that moment in time
Lymphocytes from female mice were found to produce higher levels of IFN-γ after immune stimulation than lymphocytes from males, both in vivo and in vitro (42, 43).The finding that CD8+ T cells express estrogen receptors is consistent with the estrogen-enhanced expression of the IFN-γ gene, since it was reported that CD8 cells were responsible for the majority of IFN-γ production in antigen- or mitogen-stimulated cultures of murine lymph node cells and splenocytes.
Other steroid hormones, such as cortisol or dihydoepiandrosterone (DHEA) are produced by the adrenal gland. And these hormones may affect leukocyte function directly. Sex steroids may produce different modulatory effects depending on the cytokine profile of the cells. However, it is not clear how sex steroids regulate cytokine release and the Th1/Th2 balance.
Chemokines & Th1/Th2 balance
Chemokines are chemotactic cytokines produced by a wide variety of cells to attract the relevant lymphocytes to the appropriate sites in the body. Th1 and Th2 cells express different chemokine receptor profiles. Th1 cells are thought to preferentially express the CC chemokine receptors CCR1, CXCR3, and CCR5. Chemokines, including thymus and activation-regulated chemokine (TARC), are important for the regulation of inflammation and IgE synthesis. Because TARC is responsible for trafficking of Th2 lymphocytes into sites of allergic inflammation, increases in TARC promote Th2 trafficking and, through this activity, increase IgE sensitization and asthma severity =. In a recent study the regulation of chemokine production from Th1 or Th2 lymphocyte populations indicated that there was a differential chemokine response that depended on regulation by the STAT6 (signal transducers and activators of transcription 6)-mediated pathways.
The role of chemokines in allergic disease progression is evident at multiple levels, including differential leukocyte recruitment and local cellular activation. Therefore, chemokines could control and direct the migration and activation of various leukocyte populations. Targeting chemokines should lead to new ways of controlling the inflammatory immune response.
Transcription factors & Th1/Th2 balance
Several factors determine the fate of activated T cells, type of antigen presenting cells, co-stimulatory molecules, and most importantly, cytokines present in the local environment of the cell at the time of stimulation. T-box expressed in T cells (T-bet) and GATA-binding protein 3 (GATA-3) are two major T helper-specific transcription factors that regulate the expression of Th1 or Th2 cytokine genes and play a crucial role in T-helper cell differentiation. T-bet, a newly discovered Th1-specific transcription factor is thought to initiate Th1 development while inhibiting Th2 cell differentiation. GATA-3 is a member of the GATA family of zinc finger proteins (so-called because they bind to consensus DNA sequence, A/T; GATA A/G), and plays a pivotal role in the development of the Th2 phenotype while inhibiting Th1 cells
Among the many signals that influence the development of Th cells, two have been suggested to be master regulators of Th1 and Th2 differentiation, respectively, expression of the transcription factors, T-bet and GATA-3
Takumi et al. demonstrated that overexpression of T-bet and GATA-3 regulates the development of allergeninduced airway remodeling. Serum immunoglobulin levels and cytokine analysis showed that the Th1/Th2 balance shifted toward Th1 in T-bet-tg mice and toward Th2 in GATA-3-tg mice after chronic allergen exposure. It shows that development of airway remodeling is regulated by the lung Th1/Th2 bias induced by GATA-3 and T-bet.
- Transduction pathway & Th1/Th2 balance
Signal transducer and activator of transcription molecules, or STATs, have been identified as important regulators in the transduction pathways of the interferon molecules. Especially, Th2 cytokines, IL-4 and IL-13, activate STAT1 signaling pathways across multiple cell lines. STAT1 in particular is responsive to interferon-γ, leading to the transcription of multiple genes, including principally ICAM-1 and IRF-1, both of which have been implicated in asthma.
STAT6 is another pathway in the family of STAT that has also been implicated in the development of allergic disease and asthma. Its primary activators are IL-4 and IL-13. Many have hypothesized that STAT6 might have a role in asthma, based upon its actions and location on chromosome 12
STAT6 is activated by the Th2-type cytokines, IL-4 and IL-13, it is clear that the chemokines can be controlled almost exclusively by the level of expression of the Th2-type cytokines
Allergic airways disease is initiated and perpetuated by Th2 cytokines IL-4 and IL-13, each of which induces activation of the STAT-6 transcription factor. McCusker et al. showed that the clinical manifestations of acute asthma are STAT-6 dependent, and STAT-6 is a target for drug development in allergic airways disease.
Relationship between Th1-Th2 balancing, autoimmune diseases and leptin. High leptin levels tend to shift toward Th1 and susceptibility to autoimmune disease, which could be reversed by leptin signal inhibition. Reduced leptin levels leads to susceptibility to infection and probably protection against autoimmune diseases.
In the non-obese diabetic (NOD) mouse, an animal model for type 1 diabetes (an autoimmune disease in which the pancreatic β-cells are destroyed by inflammatory processes), an increased serum level of leptin precedes diabetes in susceptible females, while injection of leptin accelerates the autoimmune destruction of the pancreatic β-cells and increases the IFN-γ production in peripheral T cells. These effects indicate that leptin promotes the development of type 1 diabetes through TH1 responses.
In MS and RA, 60 to 75% of the patients are female, and in other autoimmune diseases (thyroiditis, scleroderma, lupus erythematosus, Sjogren’s disease), 85% or more of the patients are female. This is corroborant that autoimmune diseases affect women more than men. This gender effect may, at least in part, reflect the higher average leptin concentrations in women.
Autoimmune diseases show an increasing incidence in industrialised countries compared to less developed countries. Some researchers now believe that leptin helps to determine the balance between predisposition to infections and predisposition to autoimmune diseases. This could help explain why higher circulating leptin levels predispose to autoimmune diseases and lower circulating leptin levels to infection.22 Based on the evidence regarding relationship between leptin and autoimmune diseases, leptin antagonism has been proposed as an immunotherapeutic approach for the treatment of some autoimmune disorders and even in a wider range as an effective immunosuppresant.
A model to illustrate the complex balance between T helper 1 (Th1) and Th2 cells. The Th1–Th2 paradigm hypothesises that, under the influence of a variety of factors including the cytokines interleukin 4 (IL-4) and IL-12, naive T cells can mature into one of two phenotypes, Th1 or Th2, that counter-regulate each other. This model illustrates that, in most circumstances, interaction between Th1 and Th2 cells is more complex than originally thought. These cell types probably represent extreme examples of a spectrum of phenotypes and it is possible that a cell is not committed irrevocably to one phenotype
Regulation of host resistance and disease in the response to intracellular pathogens
Intracellular bacteria and protozoa usually stimulate and are controlled by type 1 (Th1) responses. Important examples include Listeria monocytogenes, Toxoplasma gondii, Mycobacterium tuberculosis and Leishmania major (in hosts with resistant genotypes). Nevertheless, the cytokines (e.g., IFN-g, TNF-a, and IL-12) induced in the response to these agents can be quite toxic when produced in large quantity. We postulate that IL-10, a cytokine whose synthesis is also stimulated by intracellular pathogens, plays a key role in protecting the host against excessive type 1 responsiveness. Thus, when infected with a normally avirulent strain of Toxoplasma gondii, IL-10 knockout mice rapidly succumb but with no evidence of increased parasite growth. Instead, these animals show extensive tissue necrosis associated with increased synthesis of IFN-g, TNF-a, and IL-12 in either the circulation or from macrophage cultures. Thus, in the absence of IL-10 the balance is “tipped” and the normally protective immune response induced by T. gondii becomes pathogenic.
Another scenario for the induction of pathology is the abortive attempt of the immune system to control intracellular pathogens resistant to type 1 effector mechanisms. The host response to mycobacteria presents a number of excellent examples of this phenomenon. In the case of mice infected with virulent strains of Mycobacterium avium, control of bacterial growth develops only late in chronic infection and is preceded and accompanied by increasing splenomegaly. Mice with defects in macrophage function (e.g., iNOS knockout mice) fail to develop this immunopathology yet display normal IFN-g control of infection. Thus, the type 1-dependent response to infection, while attempting to limit bacterial replication, induces disease and this process becomes chronic because of the failure to eliminate the microbial stimulus.
Regulation of Th2-associated pathogenesis in helminth infection
Helminth parasites induce responses which are predominantly Th2 in character. While there is debate as to whether these responses are important in host resistance, it is clear that they can contribute to tissue pathology in several worm-triggered diseases. In schistosomiasis, Th2 cytokines dictate granuloma formation in the intravenous egg injection model and contribute with the Th1 response to the pathogenesis of granulomas and tissue fibrosis in the livers of naturally infected mice. As in intracellular infection, IL-10 is strongly induced during both murine and human schistosomiasis and appears to be responsible for containing Th1 responses and in particular IFN-g synthesis in lymphocyte cultures. Therefore, it was of interest to examine the effects of IL-10 deficiency on host pathology in this Th2-dominated disease. As expected, lymphocytes from egg-injected or S. mansoni-infected IL-10 knockout mice produced higher levels of IFN-g and reduced Th2 cytokines than wild-type cells when stimulated with egg antigens in vitro. However, the effects on pathology differed dramatically with the site of the lesion. Thus, in IL-10 knockout mice, eggs injected into the lungs were smaller than in control animals (5) while eggs laid in the liver were greater in volume. Therefore, in natural infection with this helminth, IL-10 appears to protect the host against excessive pathology, a function similar to its role in intracellular infection. Nevertheless, the mechanisms underlying this protection may be more complex than the simple regulation of Th1/Th2 function. For example, recent work suggests that B cells may exert an even more profound effect on liver granuloma formation than Th1/Th2 cytokines
Th1/Th2 balance before, during and after pregnancy
during pregnancy there is a shift from T-helper 1 (TH1 or Type 1) to T-helper 2 (TH2 or Type 2) cytokine production, followed by a “rebound” shift back to Type 1 after delivery . Type 1 cytokines (e.g. IL-12, IFN-g) are pro-inflammatory and have been implicated in the pathogenesis of several autoimmune diseases, whereas Type 2 cytokines (e.g. IL-4, IL-10, IL-13) are anti-inflammatory. It has been suggested that Type 2 cytokine production is teleologically important during pregnancy for the fetus not be immunologically rejected. Elenkov et al. recently showed that ex vivo IL-12 production after LPS stimulation is decreased during the third trimester of pregnancy and becomes increased during the postpartum period. This study further supports the notion that the rebound shift back to Type 1 cytokine production after delivery may be so extensive that autoimmune thyroid failure is triggered.
Progesterone has been shown to effect pregnancy-associated immunomodulation via alteration of the Type 1/Type 2 cytokine balance . Progesterone’s immunological effects are partially exerted through progesterone-induced blocking factor (PIBF) (a protein fraction of 34 kD). This factor is produced by progesterone-influenced lymphocytes. PIBF has immunomodulating properties that include being able to regulate perforin expression by NK cells. In addition, PIBF affects Type 1/Type 2 balance via an increased production of IL-3, IL-4, and IL-10 and decreased production of IL-12 from lymphocytes and macrophages in vitro. Treatment of mice with anti-PIBF antibody resulted in a shift toward Type 1 cytokine production along with increased rates of pregnancy resorption . The effects of estradiol on the Type 1/Type 2 balance are less clear, as both pro- and anti-inflammatory effects on CD4+ T cells by this hormone have been reported.
Type 1 versus Type 2 cytokine balance is influenced during pregnancy by cortisol as well. Pregnancy is characterized by suppression of the hypothalamic CRH neurons, due to the occurrence of hypercortisolism in the third trimester. At that time, the pituitary-adrenal unit is driven by placental CRH, which, unlike hypothalamic CRH, is positively regulated by glucocorticoids. It has been postulated that the teleological significance of the hypercortisolism of pregnancy is the suppression of the mother’s immune system so that the fetus is not rejected as a foreign body. After delivery, circulating cortisol levels decrease abruptly. This causes women to be relatively hypocortisolemic in the early postpartum state, until HPA axis activity returns to normal. The hypocortisolemic state is associated with an increase in Type 1 relative to Type 2 cytokine production. The subsequent increase in Type 1 cytokine production after delivery may be responsible for the exacerbation of certain autoimmune diseases
Nitric oxide in autoimmune disease
Nitric oxide (NO) is released locally during inflammatory autoimmune diseases and is believed to contribute to tissue destruction. However, recent studies are not fully consistent with such a simple role for NO. Here, Hubert Kolb and Victoria Kolb-Bachofen discuss data that suggest a role for NO in autoimmune diseases as an important regulator of the T helper 1 (Th1)/Th2 balance.
Th1 stimulating compounds
Echinacea, astragalus, licorice root, beta-sitosterol, ashwaganda, panax ginseng, mushrooms (Maitake, Reishi, Shiitake), chlorella, grape seed extract
Th2 stimulating compounds
Green tea, resveratrol, pycnogenol, curcumin, genistein, quercetin
Th1 and Th2 Cytokine Blood Test Panel
For those with a confirmed autoimmune condition, this is possibly the most important test. This test can point out imbalances in the immune system by looking at cytokines, proteins that the immune system relies on to communicate.
Bad communication results in complications for those with autoimmune conditions. The information this test provides can help your doctor develop a strong and effective treatment plan for you, especially when seeking alternative medicine support.
The immune system works like a seesaw. On one side Th1 cytokines that initiate the first line of defense. On the other side Th2 cytokines which help product antibodies to protect from future invasions. However, when one side goes up, the other side goes down. This can contribute to a weak immune system and potentially promote autoimmune conditions.
Running this test will help figure out where the imbalance is. Because certain botanicals used in natural medicine can boost Th1 cytokines and Th2 cytokines, this test can help develop an effective plan to help balance a weak immune system and turn the volume down on autoimmune attacks. Monitor the health of immune system with this Th1 Th2 cytokine panel along with the CD4 CD8 ratio test.
Option 1: Test can not be drawn in CA, NJ, NY, MA, MD, or RI
- Th1 cytokines (IL-2, IL-12, IFN-y, TNF-a) by Luminex Processing
- Th2 cytokines (IL-4, IL-5, IL-6, IL-10) by Luminex Processing
- Processed by Labcorp. Processing time: 3-6 weeks
Option 2: Test can not be drawn in NY. Best option for those living in the above states. You can also request it by adding “Th1/2 kit” in the additional instructions box at checkout.
- Th1 cytokines (IL-2, IL-12, IFN-y, TNF-a)
- Th2 cytokines (IL-4, IL-5, IL-6, IL-10)
- Th17 cytokines (IL-17)
- Other (TGF-b)
- Processed by NeuroSciend Labs. Processing time: 10-14 days
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