Interleukin 4 and 13 participation in mycobacterial (type-1) and schistosomal (type-2) antigen-elicited pulmonary granuloma formation: multiparameter analysis of cellular recruitment, chemokine expression and cytokine networks.
The contribution of IL-4 and IL-13 to inflammation and cytokine responses was compared in mice with types-1 or -2 pulmonary granulomas (GR) elicited by beads bound to antigens of Mycobacteria bovis (PPD) or Schistosoma mansoni eggs (SEA). Type-2 SEA-GR produced the most IL-4 and IL-13. Type-1 PPD-GR produced detectable IL-13, but not IL-4. Mice were treated with anti-IL4 or anti-IL-13 Abs, then lesion size/composition, cytokine/chemokine mRNA and lymph node cytokines were measured. Type-1 GRs resisted individual Abs, but combined Abs augmented lesions by 20%. In contrast, anti-IL-4 abrogated type-2 GR by 30-40% and eosinophil recruitment by 60%. Anti-IL-13 abrogated type-2 GR by 20-30% with no effect on eosinophils. Combined depletion reduced lesion area by 60% and eosinophils by more than 80%. In type-1 GR lungs, anti-IL-4 and anti-IL-13 augmented IFNgamma and TNFalpha mRNA. In type 2 lungs, anti-IL-13 did likewise, but anti-IL-4 decreased TNFalpha without affecting IFNgamma mRNA. In both responses, IL-4 promoted MCP-1 and MCP-5 mRNA, but IL-13 inhibited chemokines in type-1 GR. In lymph nodes, anti-IL-4, but not anti-IL-13, abrogated type-2 cytokines. In fact, IL-13 down-regulated itself and other type-2 cytokines. In summary, IL-4 and IL-13 have common and disparate regulatory functions in types 1 and 2 responses.
Ruth
J H
JH
Department of Pathology, Veterans Affairs Medical Center, Ann Arbor, MI 48105, USA.
Warmington
K S
KS
Shang
X
X
Lincoln
P
P
Evanoff
H
H
Kunkel
S L
SL
Chensue
S W
SW
D000818:Animals; D018925:Chemokines / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D015769:Granuloma, Respiratory Tract / Q000209:etiology / Q000276:immunology*; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D009163:Mycobacterium bovis / Q000276:immunology; D012333:RNA, Messenger; D011817:Rabbits; D051381:Rats; D012550:Schistosoma mansoni / Q000276:immunology; D014373:Tuberculin / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D018793:Interleukin-13; D012333:RNA, Messenger; D014373:Tuberculin; D015847:Interleukin-4