A possible novel pathway of regulation by murine T helper type-2 (Th2) cells of a Th1 cell activity via the modulation of the induction of nitric oxide synthase on macrophages.
Murine peritoneal macrophages activated with interferon (IFN)-gamma and lipopolysaccharide (LPS) produce high levels of nitric oxide (NO) and are efficient in killing the intracellular protozoan parasites Leishmania major in vitro. Earlier studies have shown that NO, whose synthesis in murine macrophages is catalyzed by an inducible enzyme NO synthase, plays a major effector role in the host resistance against microbial infection. We now shown that both the NO synthesis and the leishmanicidal activity can be inhibited by prior treatment of the cells with recombinant interleukin 4 (IL4). IL4 treatment had no effect on the binding of IFN-gamma to macrophages but prevented the induction of NO synthase in these cells activated with IFN-gamma and LPS. Since IFN-gamma is produced by murine T helper type-1 (Th1) cells, whereas IL4 is secreted by Th2 cells, these results suggest a novel pathway by which Th2 cells regulate an activity of Th1 cells, namely by inhibiting the induction of NO synthase. These results may also account for the mechanism by which the disease-promoting Th2 cells counteract the host-protective effect of Th1 cells in leishmaniasis and other intracellular parasitic diseases.
Liew
F Y
FY
Wellcome Research Laboratories, Beckenham, Kent, Great Britain.
Li
Y
Y
Severn
A
A
Millott
S
S
Schmidt
J
J
Salter
M
M
Moncada
S
S
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007895:Leishmania tropica / Q000276:immunology*; D008070:Lipopolysaccharides; D008211:Lymphocyte Cooperation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D051379:Mice; D008808:Mice, Inbred CBA; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013997:Time Factors
D008070:Lipopolysaccharides; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases