Analysis of granuloma formation in double cytokine-deficient mice reveals a central role for IL-10 in polarizing both T helper cell 1- and T helper cell 2-type cytokine responses in vivo.
In response to i.v.-injected eggs of Schistosoma mansoni, normal mice develop a dominant type 2 response, whereas IL-10-deficient animals generate a mixed type 1/type 2 cytokine profile and show reduced pulmonary granuloma formation. IL-4-deficient mice, while displaying diminished type 2 responses and granulomatous inflammation, also do not fully default to a type 1 cytokine profile. Strikingly, mice doubly deficient in IL-4 and IL-10 are completely defective in pulmonary granuloma formation and develop a highly polarized type 1 cytokine pattern. In analogous fashion, mice deficient in both IL-12 and IL-10 generate highly exacerbated type 2 cytokine responses, whereas in wild-type animals, IL-12 depletion minimally effects egg-induced cytokine production. Together, these results argue first that IL-10 is an important endogenous down-regulator of type 2 as well as type 1 cytokine synthesis, and second, that its induction is critical for type 2 response polarization in vivo.
Wynn
T A
TA
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-0425, USA. twynn@pop.niaid.nih.gov
Morawetz
R
R
Scharton-Kersten
T
T
Hieny
S
S
Morse
H C
HC
Kühn
R
R
Müller
W
W
Cheever
A W
AW
Sher
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006099:Granuloma / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D018664:Interleukin-12 / Q000276:immunology; D015847:Interleukin-4 / Q000172:deficiency; D008174:Lung Diseases, Parasitic / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012552:Schistosomiasis / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4