The H2(b) haplotype modifies the production of pro-inflammatory cytokines: implications for immunopathology.

Congenic strains of mice which differ only in their H2 haplotype were used to examine the effects of MHC genes on production of pro-inflammatory cytokines, as we have shown previously that H2(b) mice produce low levels of T cell cytokines compared to congenic H2(k) and H2(d) mice. RNase protection assays were used to assess cytokine mRNA and cytokine protein was assessed by ELISA or bioassay. Concanavalin A or phorbol myristate acetate/calcium ionophore/anti-CD3 stimulation of spleen cells from H2(b) congenic mice induced less IL-1, IL-2, IFN-gamma and MIF mRNA and/or protein than the equivalent cells from H2(d) mice. However, following stimulation with lipopolysaccharide or phorbol myristate acetate/calcium ionophore, peritoneal cells from H2(b) mice synthesised significantly more IL-1 beta, TNF-alpha, TNFR and IFN-gamma protein and IFN-gamma mRNA than cells from congenic H2(k) or H2(d) mice. These differences were evident in congenic C57BL/10 and/or BALB/c strains. We suggest that the low IL-1 production in H2(b) spleen cultures is secondary to lower T cell activation. Evidence that the H2(b) haplotype carries an immunoregulatory allele which affects cytokine production warrants further investigation.