Interleukin-4 inhibits secretion of interleukin-1beta in the response of human cells to mycobacterial heat shock proteins.
Cellular activation induced by Mycobacterium bovis bacillus Calmette-Guérin (BCG) and heat shock proteins (HSP) leads to the production of proinflammatory cytokines such as interleukin-1beta (IL-1beta) and IL-6. In this study, we found that IL-4 significantly suppressed IL-1beta secretion induced by BCG and the 70- and 65-kDa HSP. When exogenous recombinant human IL-4 was added to human mononuclear cells, a dose- and time-related inhibition of the 70-kDa HSP- and BCG-induced IL-1beta secretion was observed. IL-1beta secretion was maximally inhibited at 24 h of culture, and this inhibitory effect was sustained at a later time point of culture (120 h). In addition, IL-2, another T-cell-derived cytokine acting on monocytes, had no effect on IL-1beta secretion induced by either BCG or the 70-kDa HSP, indicating that in these experiments not all cytokines could immunoregulate IL-1beta secretion. This inhibitory effect was not due to a cytotoxic effect of IL-4, since the viabilities of human mononuclear cells were comparable in the presence and absence of IL-4. IL-4 was also able to inhibit the secretion of IL-1beta by mycobacterium-stimulated cells from three rheumatoid arthritis patients. This inhibitory effect of IL-4 was reversed with a blocking anti-IL-4 antibody. Finally, IL-4 inhibited IL-6 secretion by mycobacterium-activated human cells. These results suggest that IL-4 may be important in the regulation of the immune response to mycobacterial antigens.
Méndez-Samperio
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P
Departamento de Immunología, Escuela Nacional de Ciencias Biológicas, I.P.N. Carpio y Plan de Ayala, México, D.F. Mexico.
Badillo-Flores
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Nuñez-Vazquez
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A
Hernandez Garay
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M
D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D001500:BCG Vaccine / Q000494:pharmacology*; D002478:Cells, Cultured; D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D013268:Stimulation, Chemical
D001500:BCG Vaccine; D018840:HSP70 Heat-Shock Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D015847:Interleukin-4