Nippostrongylus brasiliensis: Ability of plasma to prime free radical generation by leukocytes in response to adult worms not due to γ-interferon or tumour necrosis factor

Abstract

Plasma-borne factors prime leukocytes from both infected and uninfected rats for radical generation in response to N. brasiliensis. The concentration of these factors is increased following infection and reaches maximal levels on day 8 post-infection (p.i.) as demonstrated by the striking ability of plasma from infected rats to prime leukocytes from uninfected rats to produce free radicals in response to adult worms. The cytokines, γ-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, including radical generation, weight loss, anaemia and diarrhoea, implicate generation of these proteins in response to infection with N. brasiliensis. We therefore investigated whether γ-interferon and TNF were detectable in the plasma of rats infected with N. brasiliensis and whether the presence of these cytokines correlated with the ability of plasma to enhance radical generation in response to N. brasiliensis. However, γ-interferon was not detected in the plasma of rats at any time after infection with N. brasiliensis and neutralizing monoclonal antibody to rat γ-interferon had no effect on the ability of plasma 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 copius in vivo synthesis of TNF could be induced by treatment of the infected rats with lipopolysaccharide (LPS). However, neither parasite-induced nor parasite plus LPS-induced plasma TNF correlated with the ability of plasma to enhance radical generation in response to N. brasiliensis. 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 levels only on days 8–14 p.i., when TNF was not detectable in plasma. Moreover, 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 γ-interferon or TNF in the plasma of infected rats does not account for the ability of plasma to prime leukocytes for free radical production in response to N. brasiliensis. However, it is distinctly possible that TNF may be involved in the diarrhoea, anaemia, weight loss and possibly other pathophysiological consequences of infection which occur on or about day 8 p.i. and thus possibly represent downstream effects of the peak levels of TNF seen in plasma on day 7 p.i.