Interleukin-6 production in a murine model of Pneumocystis carinii pneumonia: relation to resistance and inflammatory response.
The production of interleukin-6 (IL-6) and its possible relationship to host resistance and inflammatory response to Pneumocystis carinii infection were examined in mice with severe combined immunodeficiency (SCID mice). IL-6 activity was detected in the serum and lungs of P. carinii-infected mice but not in mice free of P. carinii. Moreover, the IL-6 levels in P. carinii-infected mice increased markedly after spleen cell reconstitution but then decreased to an undetectable level after the clearance of P. carinii. However, neutralization of IL-6 activity in spleen cell-reconstituted SCID mice by treatment with anti-IL-6 immunoglobulin G (IgG) resulted in no significant effect on the clearance of P. carinii (P > 0.05). Both the serum and lungs of treated mice contained an excess amount of anti-IL-6 IgG and lacked detectable IL-6. These results suggest that failure to inhibit the P. carinii clearance by anti-IL-6 treatment was not due to insufficient administration of antibody or incomplete neutralization of IL-6 activity. However, compared with mice receiving rat control IgG, mice treated with anti-IL-6 IgG had significantly higher numbers of neutrophils and lymphocytes (particularly CD8+ cells) in the lung lavage fluids (P < 0.05 for both) at day 19 after reconstitution. In addition, the levels of both total IgG (P < 0.001) and P. carinii-specific antibodies (P < 0.05) in the serum of mice treated with anti-IL-6 were significantly higher than those in control mice. These results indicate that although P. carinii infection causes both local and systemic production of IL-6 in SCID mice, IL-6 does not appear to play a crucial role in the clearance of P. carinii. However, it appears that during resolution of P. carinii pneumonia, IL-6 plays a role in the regulation of pulmonary inflammation and antibody responses.
Chen
W
W
Trudeau Institute, Inc., Saranac Lake, New York 12983.
Havell
E A
EA
Gigliotti
F
F
Harmsen
A G
AG
D000210:Acute-Phase Reaction / Q000378:metabolism*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D011020:Pneumonia, Pneumocystis / Q000276:immunology*
D007074:Immunoglobulin G; D015850:Interleukin-6