Activation of rat pulmonary lavage cells by intratracheal administration of polyinosinic-polycytidilic acid.
Systemic administration of biologic response modifiers (BRMs) is often limited by serious adverse effects. Local delivery of a BRM may provide a means to avoid systemic side effects while enhancing host defense. To test this hypothesis, the effects of intratracheal administration of the interferon inducer polyinosinic-polycytidilic acid (Poly-I:C) were examined. We demonstrated that intratracheal administration of Poly-I:C in rats results in alterations in pulmonary lavage cell number, population distribution, and function, suggestive of cellular activation. Following intratracheal instillation of 15, 75, or 150 mg of Poly-I:C, we observed a dose-dependent increase in Fc receptor-mediated phagocytosis, a dose-independent tumoricidal activity directed against xenogeneic P815 murine mastocytoma target cells, and a dose-independent decrease in superoxide anion (O2-) generation. With the exception of O2- generation, these functions returned to normal control levels by 7 days after a single dose of Poly-I:C. Thus, localized administration of Poly-I:C enhanced the host defense capability of pulmonary lavage cells, providing a rationale for compartmentalized immunoprophylaxis in the lung.
Weiss
R A
RA
Department of Experimental Pathology, Smith Kline and French Laboratories, King of Prussia, PA 19406-0939.
Meunier
P C
PC
Kelley
A
A
Klinkner
A
A
Badger
A M
AM
Bugelski
P J
PJ
D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004912:Erythrocytes; D007249:Inflammation; D007442:Intubation, Intratracheal; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D009895:Opsonin Proteins; D010587:Phagocytosis / Q000187:drug effects; D011070:Poly I-C / Q000008:administration & dosage / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000276:immunology*; D051381:Rats; D011916:Rats, Inbred F344; D011961:Receptors, Fc / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D009895:Opsonin Proteins; D011961:Receptors, Fc; D013481:Superoxides; D011070:Poly I-C