Macrophage activation and host augmentation against Sendai or herpes simplex virus (HSV) infections with synthetic polypeptides in mice

Abstract

Poly- L-Lys (mean mol. wt; 12,000), poly- L-Arg (5000) and poly- L-Orn were found to activate peritoneal macrophages effectively in vivo in 14 synthetic homo polypeptides. The ability of sequential poly( L-Arg- L-X) (5000) to activate macrophages was less than that of poly- L-Arg. Neither ( L-Arg) 12 nor ( L-Arg) 6 by themselves activated macrophages, but poly- D-Arg (5000) did, as also did poly- L-Arg; this suggests that the polycationic character of poly- L-Arg plays a role in the activation of macrophages. The intranasal administration of poly- L-Lys, - L-Arg, - L-Orn, - D-Arg, all of which activated macrophages, augmented host resistance against Sendai virus infection in mice. The protection afforded by poly- L-Arg seemed to depend on its mol. wt: the order of protection was poly- L-Arg>( L-Arg) 12>( L-Arg) 6. The intranasal administration of poly- L-Arg 3 days before the infection was effective, while that 1 day before infection was not. There was no difference between the groups in the titer of interferon produced by the infection of Sendai virus given with poly- L-Arg either 3 days before or 1 day before the infection. The administration of poly- L-Arg 3 days before the infection caused a significant decrease of the virus titer in the lung 6 days after the infection when compared with the control or the mice given 1 day before. The intravenous administration of 2-chloroadenosine (2-Cl-Ade), which is a selective inhibitor of macrophages, into the mice which had received poly- L-Arg intranasally 3 days before the infection caused a significant decrease in the survival rate of the mice, indicating that the macrophages activated with poly- L-Arg are likely to be an important element in affording the protection. Subcutaneous administration of poly- L-Arg revealed protective activity against systematic infection with herpes virus-type 1.