Effect of slow release IL-12 and IL-10 on inflammation, local macrophage function and the regional lymphoid response during mycobacterial (Th1) and schistosomal (Th2) antigen-elicited pulmonary granuloma formation.
OBJECTIVE
This study examines the local and regional effects of exogenously administered interleukins 10 (IL-10) and 12 (IL-12) on pulmonary granulomas mediated by Th1/type 1-(IFN-gamma) and Th2/type 2-(IL-4, IL-5 cytokines. MATERIALS AND TREATMENTS: Granulomas (GR) were induced in presensitized CBA mice by embolization of beads coated with Mycobacteria tuberculosis or Schistosoma mansoni egg antigens. Before challenge, osmotic pumps distributing IL-10 or IL-12 (50 micrograms/kg/day) were implanted intraperitoneally, then GR and draining lymph nodes were examined 4 days.


METHODS
GR sizes and composition were determined by morphometry and differential analysis. Isolated GR macrophages and draining lymph nodes were assessed for cytokine production by ELISA.


RESULTS
IL-10 did not effect GR sizes but reduced neutrophils in type 1 GR. IL-12 minimally reduced type 1 GR but decreased the type 2 lesion by up to 70%, primarily curtailing eosinophils. Type 2 GR macrophages were unaffected but type 1 were impaired by IL-10. Conversely, type GR macrophages were more resistant to IL-12 while type 2 showed enhanced IL-10, IL-12 and TNF, but reduced MCP-I production. In lymph nodes, IL-10 caused paradoxical effects, enhancing IFN-gamma in the type 1 and decreasing Th2 cytokines in the type 2 response. Exogenous IL-12 profoundly augmented IFN-gamma and abrogated type 2 cytokines while inhibiting intrinsic IL-12 production in lymph nodes.


CONCLUSIONS
These findings provide novel information regarding cytokine regulation and the effects of systemic cytokine therapy.
Chensue
S W
SW
Department of Pathology and Laboratory Medicine, Veterans Affairs Medical Center, Ann Arbor, MI 48105, USA.
Warmington
K
K
Ruth
J H
JH
Kunkel
S L
SL
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology; D003692:Delayed-Action Preparations; D005260:Female; D006099:Granuloma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D016753:Interleukin-10 / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000627:therapeutic use*; D008171:Lung Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D009169:Mycobacterium tuberculosis / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000942:Antigens, Bacterial; D000947:Antigens, Helminth; D003692:Delayed-Action Preparations; D016753:Interleukin-10; D018664:Interleukin-12