TUMOR-NECROSIS-FACTOR AND INTERLEUKIN-1 SYNERGY IN THE CONTEXT OF MALARIA PATHOLOGY

Reports linking human malarial illness and pathology with serum tumor necrosis factor (TNF) levels are now common, although the association is not always precise. Possible reasons for this discrepancy include t he reported variation in levels of interleukin-1 (IL-1), a cytokine kn own to synergize with TNF. We have examined the extent of synergy betw een recombinant human TNF and either recombinant human IL-1 alpha or r ecombinant human IL-1 beta in producing hypoglycemia and increasing pl asma levels of nitric oxide in malaria (Plasmodium vinckei)-infected C BA mice. Very low concentrations of either IL-1 alpha or IL-1 beta, wi th negligible effects on their own, greatly enhanced the effectiveness of TNF in bringing about these changes. In particular, synergy in gen erating nitric oxide, a mediator argued to induce cerebral malaria, wa s profound. Thus, variation in generation of IL-1 during infection pro vides one explanation for the poor correlation sometimes encountered b etween serum TNF levels and clinical condition.