Reduced Interleukin-2 Production Research Articles

Decreased interleukin-2 production in murine acute pancreatitis: Potential for immunomodulation

BACKGROUND & AIMS: The role of the cytokine interleukin 2 (IL-2) has long been recognized as central to normal immunologic function and defense against infection after burns and trauma, but little effort has been directed towards its role in acute pancreatitis (AP), which also has a high mortality related to sepsis. This study investigated the potential role of IL-2 in mice with diet-induced AP. METHODS: AP was induced in mice by 10 days of feeding a choline-deficient, ethionine- supplemented diet. T-helper (CD4) cells were estimated, and T-cell mitogen-stimulated splenocyte proliferation and IL-2 production in vitro were measured on days 3, 7, and 10. RESULTS: Significant reduction in IL-2 production was found on day 3 (32%; P < 0.05) and day 10 (48%; P < 0.005). Administration of intraperitoneal lipopolysaccharide on day 10 was associated with reduced IL-2 production (P < 0.025) 4 hours later and 90% mortality in animals with AP. In vivo therapy with recombinant IL-2 improved in vitro IL-2 secretion (P < 0.05) and reduced lipopolysaccharide-induced mortality (P = 0.036). CONCLUSIONS: Murine diet-induced AP is associated with impaired immune function and increased susceptibility to sepsis and may be a valuable tool in the investigation of immunomodulation in AP. (Gastroenterology 1996 Feb;110(2):583-8)

Estrogen inhibits interleukin-6 production and gene expression in a human osteoblastic cell line with high levels of estrogen receptors.

Some studies suggest that estrogen acts on bone by decreasing the production of interleukin-6 (IL-6), a cytokine that increases bone resorption, by osteoblasts or bone marrow cells. However, other studies have not confirmed this, possibly because of a low and variable number of estrogen receptors (ER) in the model systems used. Thus, we employed a recently developed human fetal osteoblast cell line with high levels of ER. Treatment (n = 4 experiments) with 0.01 to 10 nM of 17 beta-estradiol had no effect on the constitutive production of IL-6. However, stimulated production, induced by treatment with IL-1 beta plus tumor necrosis factor-alpha (TNF-alpha), was reduced in a dose-dependent manner to 74 +/- 3% (mean +/- SEM) of control (p < 0.01). This response was blocked by cotreatment with the type II antiestrogen ICI 182,780. Treatment with hydrocortisone (1 microM), a known inhibitor of IL-6 production in many cell types, reduced IL-6 production to 17 +/- 1% of control (p < 0.001). As assessed by Northern analysis, treatment (n = 3 experiments) with 0.01-10 nM of 17 beta-estradiol decreased steady-state levels of IL-6 mRNA in a dose-dependent manner. These data support the hypothesis that at least part of the antiresorptive action of estrogen in humans is mediated by decreased production of IL-6 by osteoblastic cells.

Anti‐inflammatory effects of Stephania tetrandra S. Moore on interleukin‐6 production and experimental inflammatory disease models

Deregulation of interleukin-6 (IL-6) expression caused the synthesis and release of many inflammatory mediators. It is involved in chronic inflammation, autoimmune diseases, and malignancy. Stephania tetrandra S. Moore is a Chinese medicinal herb which has been used traditionary as a remedy for neuralgia and arthritis in China. To investigate the anti-inflammatory effects of S. tetrandra S. Moore in vitro and in vivo, its effects on the production of IL-6 and inflammatory mediators were analysed. When human monocytes/macrophages stimulated with silica were treated with 0.1–10 μg/ml S. tetranda S. Moore, the production of IL-6 was inhibited up to 50%. At these concentrations, it had no cytotoxicity effect on these cells. It also suppressed the production of IL-6 by alveolar macrophages stimulated with silica. In addition, it inhibited the release of superoxide anion and hydrogen peroxide from human monocytes/macrophages. To assess the anti-fibrosis effects of S. tetrandra S. Moore, its effects on in vivo experimental inflammatory models were evaluated. In the experimental silicosis model, IL-6 activities in the sera and in the culture supernatants of pulmonary fibroblasts were also inhibited by it. In vitro and in vivo treatment of S. tetrandra S. Moore reduced collagen production by rat lung fibroblasts and lung tissue. Also, S. tetrandra S. Moore reduced the levels of serum GOT and GPT in the rat cirrhosis model induced by CCL4, and it was effective in reducing hepatic fibrosis and nodular formation. Taken together, these data indicate that it has a potent anti-inflammatory and antifibrosis effect by reducing IL-6 production.

Bone marrow fibroblasts from children with aplastic anemia exhibit reduced interleukin-6 production in response to cytokines and viral challenge.

Defects of the bone marrow microenvironment have been implicated in the pathogenesis of aplastic anemia (AA). We examined granulocyte/macrophage colony-stimulating factor (GM-CSF) and IL-6 production in bone marrow fibroblasts from five children with AA in response to cytokines and viral challenge with cytomegalovirus (CMV). Cytokine-stimulated IL-6 production in patients' fibroblasts was significantly reduced, whereas GM-CSF production was found to be comparable to normal controls. Also, CMV-mediated stimulation of IL-6 production was significantly lower in bone marrow fibroblasts from patients with AA. During the late phase of CMV-infection, IL-6 production was suppressed in CMV-infected fibroblasts from patients with AA with 90% inhibition of IL-6 protein production and marked reduction in IL-6 mRNA accumulation. Defective IL-6 production in bone marrow fibroblasts might contribute to hematopoietic suppression in some patients with AA.

Role of interleukin-8 (IL-8) and an inhibitory effect of erythromycin on IL-8 release in the airways of patients with chronic airway diseases

To evaluate of the role of interleukin-8 (IL-8), a chemotactic cytokine, in the continuous neutrophil accumulation in the airways of patients with chronic airway disease (CAD) and persistent Pseudomonas aeruginosa infection, we investigated the cell population, IL-8 levels, IL-1 beta levels, tumor necrosis factor (TNF) activities, and neutrophil elastase (NE) activities of bronchoalveolar lavage (BAL) fluids in 17 CAD patients (with P. aeruginosa infections [CAD+PA], n = 9; without any bacterial infections [CAD-PA], n = 8) and 8 normal volunteers. We found significant elevations of neutrophil numbers, IL-8/albumin ratios, and NE/albumin ratios in BAL fluids from CAD patients, in the following rank order: CAD+PA > CAD-PA > normal volunteers. IL-1 beta/albumin ratios were elevated only in CAD+PA, while no TNF bioactivity was detected in BAL fluids. The neutrophil numbers correlated significantly with the IL-8/albumin ratios and NE/albumin ratios in the BAL fluids of CAD patients. When anti-human IL-8 immunoglobulin G was used for neutralizing neutrophil chemotactic factor (NCF) activities in BAL fluids, the mean reduction rate of NCF activities in CAD+PA patients was significantly higher than that in CAD-PA patients. We also evaluated the effects of low-dose, long-term erythromycin therapy in BAL fluids from three CAD+PA and two CAD-PA patients. Treatment with erythromycin caused significant reductions of neutrophil numbers, IL-8/albumin ratios, and NE/albumin ratios in BAL fluids from these patients. To elucidate the mechanism of erythromycin therapy, we also examined whether erythromycin suppressed IL-8 production by human alveolar macrophages and neutrophils in vitro. We demonstrated a moderate inhibitory effect of erythromycin on IL-8 production in Pseudomonas-stimulated neutrophils but not in alveolar macrophages. Our data support the view that persistent P. aeruginosa infection enhances IL-8 production and IL-8-derived NCF activity, causing neutrophil accumulation in the airways and the progressive lung injuries observed in patients with CAD. The clinical efficacy of erythromycin therapy for CAD patients might be partly mediated through a reduced IL-8 production, diminishing neutrophil accumulation and NE release in the airways.

Spontaneous in vitro differentiation of a myoepithelial cell line (PA 16/23) from a pleomorphic adenoma of the parotid gland is associated with reduced production of the autocrine growth factor interleukin 6.

A myoepithelial cell line (PA 16/23) was derived from a pleomorphic adenoma of the parotid gland. PA 16/23 cells have light microscopic, immunophenotypical and ultrastructural features of immature myoepithelial cells, i.e. they are of fusiform or stellate shape and show keratin and actin cytofilaments located mainly in the perinuclear cytoplasm, desmosomes and tracts of basal lamina. The PA 16/23 cells grew actively and expressed mRNA for and produced interleukin 6 (IL-6) which was released into the culture medium. This cytokine, in turn, acted as an autocrine growth factor on the cells. PA 16/23 cells also expressed high-affinity IL-6 receptors. In these cells, both IL-6 production and proliferation could be modulated by exogenous stimulants, such as IL-6 itself, IL-1, IL-4, tumour necrosis factor alpha, interferon gamma and lipopolysaccharide. From the 40th culture passage onwards, the PA 16/23 cells ceased to grow, either spontaneously or in response to exogenous stimulants. Moreover, they strongly reduced IL-6 production, and underwent morphological differentiation into more mature myoepithelial cells, with an increased amount and a different arrangement of the keratin and actin cytofilaments, which formed thick bundles in the peripheral cytoplasm. These findings suggest a role for IL-6 in modulating the proliferation and, possibly, the differentiation of the PA 16/23 cells.

On the role of monokines in the generation of nonspecific suppressor T cell activity in vitro.

We examined the role of endogenously produced interleukin 1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in lectin-induced nonspecific suppressor activity in vitro. The cultures consisted of highly purified T lymphocytes, autologous monocytes and phytohemagglutinin (PHA). Kinetic studies revealed peak levels for both TNF-alpha and IL-1 beta production 4 hr after initiation of cultures which then declined and reached minimal levels on day 3. At this time point maximal levels of interleukin-2 (IL-2) were detected which declined sharply 24 hr later. The decline in cytokine levels in culture supernatants was most probably due to their consumption by the mononuclear cells which were found to express specific receptors for IL-1 beta, (IL-1 beta R), TNF-alpha (TNF-alpha R) and IL-2 (IL-2R) after 3- and 6-days of culture. After their first cycle of production and consumption both monokines were reproduced and the events followed the same patterns as for the first cycle: both monokines were first produced and at the time point of their consumption, IL-2 production reached maximal levels. The requirement for IL-1 beta and TNF-alpha in both IL-2 production and generation of suppressor activity was shown by three different approaches which included (a) blocking of HLA-DR molecules on monocytes which prevented monokine consumption during the early stages of culture, (b) blocking of HLA-A,B,C molecules on monocytes which prevented monokine consumption and IL-2 production late in culture, and (c) neutralization of monokine activity late in culture which resulted in highly reduced IL-2 production. T lymphocytes harvested from such cultures exhibited diminished suppressor activity. Our data suggest that the generation of nonspecific suppressor cell activity in vitro represents a complex system that requires cell interactions via self-major histocompatibility complex (MHC) antigen recognition and two cycles of cytokine production, where IL-1 beta and TNF-alpha production and consumption is a prerequisite for IL-2 production. Since lectin-induced nonspecific suppressor activity in vitro is deficient in certain autoimmune disorders the data presented herein might help in understanding the cellular basis for this immunodeficiency.

Regulation of rat pulmonary endothelial cell interleukin-6 production by bleomycin: effects of cellular fatty acid composition.

Previous studies have shown upregulation of lung cell interleukin-6 (IL-6) production in bleomycin-induced pulmonary fibrosis. To further elucidate the regulatory mechanisms governing this disease, the effects of bleomycin on the production of the pleiotropic cytokine, IL-6, were investigated in lung endothelial cells. Rat pulmonary artery endothelial cells were treated with bleomycin at doses previously shown to be effective in upregulating cytokine production in these cells, and the conditioned media was collected and assayed for IL-6 activity. The results show that these endothelial cells constitutively produced IL-6 and that bleomycin increased the production in a time- and dose-dependent manner. Feeding rats diets deficient in n-6 fatty acids is known to ameliorate bleomycin-induced lung fibrosis. In order to examine if fatty acids could modulate IL-6 production in vitro, cells were lipid depleted and then supplemented with 18:1n-9, 18:2n-6, or 18:3n-3 fatty acids, and the effects of bleomycin on IL-6 production reexamined. This regimen resulted in significant depletion of arachidonate in the 18:1n-9 and 18:3n-3 supplemented cells, which was associated with significantly reduced IL-6 production relative to the 18:2n-6-supplemented cells, both constitutively and when stimulated with bleomycin. Preincubation with indomethacin did not significantly inhibit the production of IL-6 by all three groups of cells, nor did supplementation with a stable prostacyclin analog increase IL-6 production. These results suggest that endothelial cell IL-6 production is not directly dependent on prostacyclin or other cyclooxygenase metabolites but may require or be upregulated by 18:2n-6 and/or metabolites derived from it.(ABSTRACT TRUNCATED AT 250 WORDS)

Interferon gamma inhibits interleukin 10 production by monocytes.

Interleukin 10 (IL-10) was first described for its ability to inhibit interferon gamma (IFN-gamma) production. Herein, we studied the balance between IFN-gamma and IL-10 production by human peripheral blood mononuclear cells (PBMC) in response to Staphylococcus aureus Cowan (SAC) or lipopolysaccharide (LPS). Monocyte depletion reduced IL-10 production by 90% and resulted in an increased IFN-gamma production. Addition of anti-IL-10 antibody to PBMC cultures also strongly increased IFN-gamma production. In contrast, among various cytokines, only IFN-gamma strongly reduced IL-10 synthesis by SAC- or LPS-activated PBMC and monocytes. Thus, IFN-gamma has proinflammatory effects through the combination of two mechanisms: (a) induction of early tumor necrosis factor alpha (TNF-alpha) and IL-1 beta synthesis; and (b) inhibition of the delayed production of IL-10, an inhibitor of TNF-alpha and IL-1 beta synthesis. Taken together, the present data indicate that IFN-gamma and IL-10 antagonize each other's production and function.

Low dose stretozotocin-induced diabetes in mice: Reduced IL-2 production and modulation of streptozotocin-induced hyperglycemia by IL-2

The possible role of interleukin 2(IL-2) in the pathogenesis of multiple low dose streptozotocin (Sz)-induced diabetes in mice was analysed. Spleen cells from diabetic male C57B1/6 mice showed diminished mitogen-induced IL-2 production as determined by bioassay using the IL-2-dependent T-cell line CTLL-2. In parallel the proliferative response was reduced. Systemic daily administration of human recombinant IL-2 for 3 weeks had dose-dependent effects on the development of hyperglycemia in Sz-treated (5 × 40 mg) mice: while IL-2 at doses of 1 × 2, 1 × 10, 2 × 10 μg/kg body weight caused partial suppression of hyperglycemia, higher doses (2 × 20, 2 × 40 μg/kg) had an enhancing effect. Treatment with the lowest dose (1 × 1 μg/kg) or with a control preparation from bacteria (2 × 10 μg/kg) did not significantly alter the course of diabetes. Effects of IL-2 were similar when treatment was started concomitantly with or only after streptozotocin injections. This observation argues against the direct interaction between IL-2 and streptozotocin but suggests modulation of immune reactivity by IL-2. Our findings of decreased mitogen- stimulated IL-2 production by splenic lymphocytes, and the disease-modulating effect of IL-2 in the low-dose streptozotocin diabetes extend our previous observations in spontaneously diabetic BB rats and further support the notion of an involvement of IL-2 in the control of autoimmune diseases.

Establishment of an IL-2-dependent bovine T cell line and an assay of lymphocyte response inhibition in leukemic bovine serum.

The mechanism of immunosuppression induced by leukemic bovine serum was investigated with respect to lymphokine reactions using an interleukin 2 (IL-2)-dependent bovine T cell line generated from bovine peripheral blood lymphocytes (PBLs). The suppression of concanavalin A (con A)-induced PBL blastogenesis was observed at a high rate in leukemic cattle sera. The growth of IL-2-dependent bovine T cells and IL-2 production from con A-induced bovine PBLs were also inhibited by these sera, and particularly, the latter was correlated significantly to the degree of lymphocyte blastogenesis by the mitogen. Therefore, the lesser sensitivity of lymphocytes to IL-2 and the reduced IL-2 production by activated lymphocytes seem to play a role in suppressing the lymphocyte reaction.

ヒト末梢血リンパ球機能に対するヒスタミン受容体の役割 ＩＬ‐６産生能

We examined the effects of histamine on interle-ukin-6 (IL-6) production in human peripheral blood lymphocytes (PBL) .PBL obtained from healthy volunteers were cultured in RPMI 1640 with 1% FCS for 72 hours. The effects of histamine, 2-pyridylethylamine (H1 receptor agonist) and dimaprit (H2 receptor agonist) on phyto-hemagglutinin (PHA) -driven IL-6 production and intra-cellular cyclic AMP (cAMP) accumulation were analyzed with time course.The production of IL-6 in PBL was gradually increased by 24 hours with reaching plateau after PHA activation. Both histamine and dimaprit significantly reduced the production of IL-6 in PBL, but 2-pyridylethylamine did not. The content of intra-cellular cAMP in PBL was rapidly increased after incubation with both histamine and dimaprit.These results indicated that histamine increased intra-cellular cAMP and then reduced IL-6 production in PBL through H2 receptor.

Effect of exposure to benzene on natural killer (NK) cell activity and interleukin-2 (IL-2) production of C57BL/6 mice.

To investigate the effect of benzene on murine splenic natural killer (NK) cell activity and interleukin-2 (IL-2) production, we exposed C57 BL/6 mice to benzene for 28 days. Benzene exposure via drinking water at doses of 27 and 154 mg/kg/day yielded the following results. 1) A decrease of spleen cell number was detected on the 14th day of benzene exposure at 154 mg/kg/day, and on the 21st and 28th day of exposure at both 27 mg/kg/day and 154 mg/kg/day. 2) NK activity per viable spleen cell was temporarily enhanced on the 21st day of exposure at doses of 27 and 154 mg/kg/day, thereafter returned to control levels. 3) IL-2 production was inhibited after 28 days of benzene exposure at 27 and 154 mg/kg/day. After ending exposure at doses of 27 mg/kg/day for 28 days, the decreased spleen cell number began to return to control levels from the 14th day on, and reduced IL-2 production returned to control levels. These results suggest that, NK cells are resistant to benzene toxicity, while IL-2 producing cells are sensitive. Thus, an imbalance in immune system was caused by toxic benzene action.

Capacity to produce interleukin 2 is impaired in haemophilia in the absence and presence of HIV 1 infection

Capacity to produce interleukin-2 (IL-2) was measured in haemophiliacs from a well-defined treated cohort. Patients were selected on the basis of HIV-1 antibody status, mean annual dose of clotting factor and liver disease severity. T-cell subsets and peripheral blood mononuclear cell proliferation to Mycobacterium tuberculosis purified protein derivative (PPD) were also measured. Haemophiliacs had reduced IL-2 production, independent of HIV-1 antibody status, mean annual dose of clotting factor concentrate used and liver disease severity. In HIV-1 antibody positive patients reduced levels correlated with PPD proliferative responses (r = 0.6, P = 0.04) and CD8 + ve (r = 0.5, P = 0.05) but not CD4 + ve cell numbers (r = 0.3, P = 0.2). No such correlations were seen in HIV-1 antibody negative patients. Reduced IL-2 production in HIV-1 antibody negative haemophiliacs was due to a qualitative defect. In HIV-1 positive patients a qualitative defect in T lymphocytes that selectively proliferate in response to PPD was observed. CD4 + ve cell numbers were reduced in HIV-1 positive patients.

Correlation of Serum Interleukin-2 Levels, Soluble Interleukin-2 Receptors and T Lymphocyte Subsets in Cancer Patients

An interleukin-2 (IL-2) in vitro reduced production has been observed in most metastatic cancer patients. At present, however, there are no data on blood IL-2 levels in vivo, because of the too low sensitivity of previous biological and enzyme immunoassay methods. The recent development of a sensitive RIA method allowed us to start a preliminary investigation of IL-2 production in basal conditions in human solid tumors. The study included 42 cancer patients. Breast and lung cancer were the two commonest neoplasms. Serum levels of IL-2 and soluble IL-2 receptors (SIL-2R), and CD4/CD8 ratio were measured in each patient. The control group consisted of 58 healthy subjects. Mean serum levels of IL-2 were significantly lower in metastatic patients (n = 23) than in those without metastases (n = 19). Patients with low CD4/CD8 ratio (n = 16) had significantly lower mean values of IL-2 than those with normal ratio (n = 26). Finally, mean IL-2 concentrations were significantly lower in patients with elevated levels of SIL-2R than in those with normal values. These results would suggest that metastatic dissemination is associated with a decreased IL-2 production in vivo, and that reduced IL-2 production is more frequent in patients with low CD4/CD8 ratio.

Serum levels of interleukin-2 in cancer patients: preliminary considerations.

In order to investigate the production of interleukin-2 (IL-2) in human neoplasms, we determined IL-2 and soluble IL-2 receptors (sIL-2R) in serum from 18 patients with lymphoma and 28 patients with solid tumors, with (15 cases) or without (13 cases) metastases. As controls, 58 healthy subjects were evaluated. Low levels of IL-2 were not observed in patients with lymphoma or limited solid tumor but abnormally low concentrations of IL-2 were seen in 4/15 metastatic solid tumors, associated with abnormally high values of sIL-2R. This preliminary study confirms in vivo the reduced IL-2 production in metastatic solid neoplasms, previously documented in vitro.

Pinealectomy inhibits interleukin-2 production and natural killer activity in mice

Four — five-week-old C57BL/6 mice were surgically pinealectomized. At different time intervals after surgery their spleens were removed and assayed for interleukin-2 (IL-2) production and natural killer (NK) cell activity. Non-operated and sham-operated mice were used as controls. The present results indicate that pinealectomy significantly reduced IL-2 production and NK cell activity, in comparison to sham-operated mice. These effects seem to be related to the lack of melatonin. In fact the subcutaneous injection of this hormone (50 or 100 mg/kg at 5 p.m.) in pinealectomized mice was able to restore IL-2 production and NK cell activity. However, chronic treatment with melatonin (10, 20 and 50 mg/kg for 9 consecutive days) failed to reverse the impairment of the immune responses.

Association of reduced interleukin-2 production with genetic susceptibility to Pichinde virus in inbred strains of hamsters.

Adult inbred MHA hamsters are susceptible to lethal infections with Pichinde virus while inbred LSH hamsters resist such infections. Previous studies demonstrated higher levels of endogenous and induced natural killer (NK) activity in MHA splenocytes than in LSH splenocytes. Preferential replication of Pichinde virus in cells with NK activity was suggested by showing that the greater numbers of infected spleen cells observed in MHA hamsters could be accounted for by a cell population that cosedimented with a peak of NK activity. Increased cellularity of thymi and spleens as well as increased cells sensitive to lymphokines was also found in MHA hamsters as compared to LSH hamsters. In the present study we found that injection of anti-asialo GM 1 serum reduced NK activity but did not alter susceptibility to virus infection. However, MHA hamsters were found to be relatively deficient in the production of interleukin 2 and injection of interleukin 2 altered the mortality of hamsters infected with Pichinde virus. These findings suggest that susceptibility to lethal infection by Pichinde virus is associated with reduced ability to produce interleukin 2 in MHA hamsters.

Inadequate Interleukin 2 Production

We studied the production of the two major mediators of cellular immune responses, Interleukin 1 (IL-1) and Interleukin 2 (IL-2), by the peripheral blood mononuclear cells of 23 burn patients (16 men, seven women, mean age 48.9 years) compared with 23 matched controls (16 men, seven women, mean age 46.7 years). Serial measurements were made of IL-1 production by adherent mononuclear cells after stimulation with lipopolysaccharide and of IL-2 production by lymphocytes after stimulation with phytohemagglutinin (PHA). Eighty determinations of IL-2 production by lymphocytes from 12 patients with greater than 30% body surface area burn revealed a mean IL-2 production of 0.71 u as compared with a mean of 1.23 u for patients with less than 30% burns (p = 0.04). Patients with greater than 30% body surface area burns had significantly reduced IL-2 production (p less than or equal to 0.05) until 60 days after injury, whereas those with smaller burns had reduced IL-2 production only at 20-29 and 30-39 days postburn. Nine burn patients with systemic sepsis showed significantly lower IL-2 production (p = 0.03) at 10-29 days postburn than nonseptic patients, and significantly less IL-2 production during septic episodes. Eight patients with greater than 50% suppression of lymphocyte response to PHA produced less IL-2 (0.4 u) than patients with less than 50% suppression, (1.07 u, p = 0.004). IL-1 production was significantly elevated as compared with controls (4.45 u vs. 3.6 u, p = 0.05) early after injury, but was subsequently within the normal range regardless of burn size. The percentage of circulating helper T-lymphocytes, the principal source of IL-2, was also reduced, although this did not always correlate with IL-2 production, which remained depressed after recovery of the helper T-cell population. These results indicate that failure to produce IL-2, a powerful mediator of cellular immune responses, is an important mechanism underlying the defective cell mediated immunity seen in burn patients.