Functional consequences of perceived interleukin deficiencies? Analysis employing NZB x C58 recombinant inbred mice.

NZB mice have previously been shown to be deficient in the production of interleukins 1 and 2 (IL-1, IL-2) during the development of autoimmune disease. One or both of these defects have been inherited in certain of the NZB X C58 recombinant inbred strains (N X 8 RI). Certain of these strains have been selected to examine further the effect of decreased production of IL-1 and/or IL-2. The interleukin deficiencies found in vitro were not due to the presence of an inhibitor/suppressor nor was any activity found intracellularly upon water lysis of stimulated cells. Despite profound IL-1 and/or IL-2 deficiencies measured in vitro, all of the N X 8 RI lines examined were found to be capable of producing IL-1 in vivo as shown by their serum amyloid A response to endotoxin injection. We conclude from these studies that defects in IL-1 production measured in vitro do not reflect inability to produce this lymphokine in vivo. Young, IL-1 deficient NZB mice generated CTL to TNP-self but old, IL-2 deficient NZB mice did not. Since all other strains were found to generate cytotoxic T cells to TNP-self regardless of interleukin defects, we also conclude that the cytotoxic T cell defect in NZB mice is due to some presently unknown factor in addition to IL-2 deficiency. The relationship of decreased production of interleukins to the development of autoimmunity remains undefined.