NIPPOSTRONGYLUS-BRASILIENSIS - ABILITY OF PLASMA TO PRIME FREE-RADICAL GENERATION BY LEUKOCYTES IN RESPONSE TO ADULT WORMS NOT DUE TO GAMMA-INTERFERON OR TUMOR NECROSIS

Plasma-borne factors prime leukocytes from both infected and uninfecte d rats for radical generation in response to N. brasiliensis. The conc entration of these factors is increased following infection and reache s maximal levels on day 8 post-infection (p.i.) as demonstrated by the striking ability of plasma from infected rats to prime leukocytes fro m uninfected rats to produce free radicals in response to adult worms. The cytokines, gamma-interferon and tumour necrosis factor (TNF) can be detected in plasma during infection with a variety of organisms and several lines of immunological and pathophysiological evidence, inclu ding radical generation, weight loss, anaemia and diarrhoea, implicate generation of these proteins in response to infection with N. brasili ensis. We therefore investigated whether gamma-interferon and TNF were detectable in the plasma of rats infected with N. brasiliensis and wh ether the presence of these cytokines correlated with the ability of p lasma to enhance radical generation in response to N. brasiliensis. Ho wever, gamma-interferon was not detected in the plasma of rats at any time after infection with N. brasiliensis and neutralizing monoclonal antibody to rat gamma-interferon had no effect on the ability of plasm a to prime free radical generation. TNF was detected in the plasma of heavily-infected rats but only at very low levels (<1 ng/ml), though c opius in vivo synthesis of TNF could be induced by treatment of the in fected rats with lipopolysaccharide (LPS). However, neither parasite-i nduced nor parasite plus LPS-induced plasma TNF correlated with the ab ility of plasma to enhance radical generation in response to N. brasil iensis. Thus, TNF concentrations in non-LPS-treated rats were greatest on days 4-7 p.i. but the ability of plasma to stimulate free radical generation by rat leukocytes was significantly higher than control lev els only on days 8-14 p.i., when TNF was not detectable in plasma. Mor eover, antibody to TNF had no effect on the ability of plasma to prime free radical generation in response to adult N. brasiliensis in vitro . Thus, the presence of either gamma-interferon or TNF in the plasma o f infected rats does not account for the ability of plasma to prime le ukocytes for free radical production in response to N. brasiliensis. H owever, it is distinctly possible that TNF may be involved in the diar rhoea, anaemia, weight loss and possibly other pathophysiological cons equences of infection which occur on or about day 8 p.i. and thus poss ibly represent downstream effects of the peak levels of TNF seen in pl asma on day 7 p.i.