ASSOCIATION OF INTERLEUKIN-6 IN THE PATHOGENESIS OF ACUTELY FATAL SIV(SMM PBJ-14) IN PIGTAILED MACAQUES/

Infection with a variant of simian immunodeficiency virus (SIVsmm/PBj- 14) causes death in juvenile pigtailed macaques awithin 8 days of infe ction. The primary pathology is localized to the lymphoid tissues of t he gut and spleen. Although the virus is present, the lesions are most consistent with acute reactive inflammation. We studied the serum and tissues for evidence of acute cytokine production often associated wi th acute inflammation. One factor, IL-6, was found to be significantly increased (>1000-fold) over all other measured cytokines in all the p igtailed macaques who died acutely. Increased levels of IL-6 were foun d both in the serum and in the inflamed tissues. mRNA for IL-6 was fou nd in the tissues with the highest protein levels of IL-6. The marked increase in IL-6 and IL-6 mRNA correlated with the virus levels in the tissues and serum as determined by viral isolation, immunohistochemis try, and Northern blot analysis. These findings suggest that the under lying pathogenesis of primary tissue damage, necrosis, and death by PB j-14 is the induction of cytokine production. Although the presence of the virus may be critical for the initiation of these events, the int ense inflammatory reaction is associated with the cause of death.