Role and effect of IL-2 in experimental visceral leishmaniasis.
In experimental visceral leishmaniasis, acquired resistance is T cell-dependent, involves IFN-gamma-activated macrophages, and is expressed in the tissues by granuloma formation. Resistance also correlates with Ag-stimulated IL-2 secretion; therefore, Leishmania donovani-infected BALB/c mice were treated with anti-IL-2 mAb or rIL-2 to determine the host defense effect of IL-2. In control mice, intracellular hepatic infection peaked at 2 wk and then declined coincident with granuloma development. In contrast, liver parasite burdens in anti-IL-2-treated mice continued to increase until after 4 wk, at which time mature granuloma formation was inhibited. Treatment of mice with continuously administered IL-2 reduced liver burdens by > 50% and led to marked accumulation of granuloma mononuclear cells. The IL-2-responsive mechanism was T cell-dependent and required both L3T4+ and Lyt-2+ cells. IL-2 enhanced IFN-gamma mRNA expression in vivo and was required for IFN-gamma secretion in vitro, and anti-IFN-gamma mAb administration abolished the antimicrobial effect of exogenous IL-2. These results: 1) identify the activity of endogenous IL-2 in both antileishmanial resistance and granuloma formation; 2) demonstrate that exogenous IL-2 can enhance the granulomatous tissue reaction; and 3) indicate that IL-2 treatment stimulates intracellular antimicrobial activity largely via the induction of IFN-gamma.
Murray
H W
HW
Division of Infectious Diseases, Cornell University Medical College, New York, NY 10021.
Miralles
G D
GD
Stoeckle
M Y
MY
McDermott
D F
DF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D006099:Granuloma / Q000209:etiology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma