TY - JOUR

T1 - Interferon-gamma (IFN-gamma) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats

AU - Johansen, H K

AU - Hougen, H P

AU - Rygaard, J

AU - Høiby, N

PY - 1996

Y1 - 1996

N2 - In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF), we studied whether the inflammatory response could be altered by intraperitoneal treatment with recombinant rat interferon-gamma (rrIFN-gamma). Rats were treated either before or after intratracheal challenge with P. aeruginosa embedded in alginate beads. Rats treated after challenge had a significant reduction in the severity of macroscopic lung inflammation compared with rats treated before challenge (P = 0.004) and controls (P = 0.003). The histopathology in controls was dominated by numerous polymorphonuclear leucocytes (PMN) (> or = 90%) surrounding the alginate beads like in CF. This could be caused by a Th2-like response. In contrast, a complete shift to a chronic-type inflammation dominated by mononuclear leucocytes (> or = 90% lymphocytes and plasma cells) and granulomas was observed in both rrIFN-gamma-treated groups of rats. This could be caused by a Th1-like response. There was no significant difference in lethality between the groups, and the antibody titres against P. aeruginosa sonicate and alginate were similar in the treated rats and controls. Since the ongoing lung tissue damage in CF patients has been shown to be caused by elastase secreted by PMN, which dominate the P. aeruginosa lung infection, our findings offer a possible new strategy of modifying the inflammatory response in CF patients.

AB - In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF), we studied whether the inflammatory response could be altered by intraperitoneal treatment with recombinant rat interferon-gamma (rrIFN-gamma). Rats were treated either before or after intratracheal challenge with P. aeruginosa embedded in alginate beads. Rats treated after challenge had a significant reduction in the severity of macroscopic lung inflammation compared with rats treated before challenge (P = 0.004) and controls (P = 0.003). The histopathology in controls was dominated by numerous polymorphonuclear leucocytes (PMN) (> or = 90%) surrounding the alginate beads like in CF. This could be caused by a Th2-like response. In contrast, a complete shift to a chronic-type inflammation dominated by mononuclear leucocytes (> or = 90% lymphocytes and plasma cells) and granulomas was observed in both rrIFN-gamma-treated groups of rats. This could be caused by a Th1-like response. There was no significant difference in lethality between the groups, and the antibody titres against P. aeruginosa sonicate and alginate were similar in the treated rats and controls. Since the ongoing lung tissue damage in CF patients has been shown to be caused by elastase secreted by PMN, which dominate the P. aeruginosa lung infection, our findings offer a possible new strategy of modifying the inflammatory response in CF patients.

KW - Animals

KW - Cystic Fibrosis

KW - Disease Models, Animal

KW - Female

KW - Inflammation

KW - Interferon-gamma

KW - Pneumonia, Bacterial

KW - Pseudomonas Infections

KW - Rats

KW - Rats, Inbred Lew

KW - Recombinant Proteins

KW - Th1 Cells

M3 - Journal article

C2 - 8565302

VL - 103

SP - 212

EP - 218

JO - Clinical and Experimental Immunology, Supplement

JF - Clinical and Experimental Immunology, Supplement

SN - 0964-2536

IS - 2

ER -