L‐Arginine‐dependent destruction of intrahepatic malaria parasites in response to tumor necrosis factor and/or interleukin 6 stimulation

There is growing evidence that cytokines (interleukin [IL] 1, IL 6, interferon‐γ, tumor necrosis factor [TNF]) directly or indirectly interfere with the intrahepatic development of malaria parasites. Recent work in our laboratory clearly showed that TNF can affect the hepatic development of parasites via IL 6 secreted by liver nonparenchymal cells. The possible participation of an L‐arginine‐dependent effector mechanism has been studied to explain the TNF/IL 6‐induced inhibition. We thus investigated if NGmonomethyl‐L‐arginine and Nω‐nitro‐L‐arginine, two specific inhibitors of inorganic nitrogen oxide synthesis from L‐arginine, were able to affect the inhibitory effect of TNF and/or IL 6 in co‐cultures. At 0.1 and 0.5 mM both L‐arginine analogues reversed the inhibitory effect of these cytokines. An interesting observation is that L‐arginine analogues enhance schizont development in the absence of prior cytokine contact. This result indicates an hepatic basal L‐arginine‐dependent anti‐parasitic activity which might explain the existence of self‐degenerating hepatic forms as previously reported.