Tumor necrosis factor plays a role in Schistosoma mansoni egg-induced granulomatous inflammation.
In murine schistosomiasis mansoni several proinflammatory lymphokines participate in the circumoval granulomatous inflammatory response. At the acute stage of the infection lymphokine secretion is maximal and coincides with the strong granulomatous reaction. With chronicity, Ag-elicited lymphokine production diminishes and the granulomatous inflammation is downmodulated. In this study the role of TNF in the granulomatous response was investigated. Macrophages isolated from vigorous liver granulomas of acute infection mice on LPS stimulation produced significantly more TNF than their counterparts obtained from the downmodulated granulomas of chronic infection animals. Endotoxin-injected, acutely infected mice had higher TNF serum levels than those with chronic infection. Repeated injections of polyclonal anti-TNF-alpha antiserum given to acutely infected mice significantly suppressed the size of developing liver granulomas. Administration of graded dosages of recombinant murine TNF-alpha to mice with chronic infection restored the size of the downmodulated liver and lung granulomas to the level of the vigorous lesions. Repeated injections of rIL-2 to chronically infected mice augmented the downmodulated liver granulomatous response, induced enhanced production of TNF by the liver granuloma macrophages, and elevated cytokine levels in the sera of treated mice. Enhanced TNF production was also observed in vitro in monolayers of murine rIFN-gamma-treated granuloma macrophages. These findings indicate that focally and systemically produced TNF influences the development of the schistosome egg-induced granulomatous response. Moreover, in vivo manipulation of cytokine levels can modify the intensity of the inflammatory response.
Joseph
A L
AL
Department of Surgery, Wayne State University School of Medicine, Detroit, MI 48201.
Boros
D L
DL
D000818:Animals; D005260:Female; D006099:Granuloma / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology; D008099:Liver / Q000276:immunology; D008109:Liver Diseases, Parasitic / Q000276:immunology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D010063:Ovum / Q000276:immunology*; D011817:Rabbits; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha