title: Effect of selected cytokines on the replication of Corynebacterium pseudotuberculosis and ovine lentiviruses in pulmonary macrophages.
abstract: Opportunistic bacterial pathogens that induce monokine secretion by pulmonary alveolar macrophages (PAM) are frequently encountered complicating factors in lentivirus-associated pneumonias in ungulates and man. We examined the effect of selected cytokines on the replication of Corynebacterium pseudotuberculosis and ovine lentivirus (OvLV) in ovine PAM. Recombinant bovine (rBo) IL 1 beta, rBoIL-2, rBo interferon-gamma (IFN gamma) and rBoTNF alpha, alone and in combination at physiological doses had no apparent effect on the extracellular growth of C. pseudotuberculosis, compared with the growth of the pathogen in medium alone. Untreated ovine PAM, derived from bronchoalveolar lavage, were found to substantially reduce, but not eliminate the growth of C. pseudotuberculosis in culture. This bactericidal effect was neither enhanced nor inhibited by pretreatment of PAM with the recombinant bovine cytokines or low doses of LPS that induce monokines. In contrast, addition of rBoTNF alpha or rBoIL-1 beta, at physiological doses, at the initiation of, or on Day 4, after OvLV infection resulted in a significant increase in viral replication in PAM, as measured in an antigen capture assay for OvLV p25, compared with untreated infected cells. This effect was more pronounced with lower levels of infecting OvLV, and, in the case of TNF alpha, was abrogated by preincubation of the cytokine with specific anti-serum. Conversely, in most instances, inclusion of rBoIFN alpha in OvLV-infected PAM cultures resulted in a significant decrease in viral replication. These results suggest that these soluble mediators that are probably secreted in response to C. pseudotuberculosis infection may have little direct effect on the extra- or intracellular survival of the bacteria in the lung, but may modulate lentiviral replication and, by extension, disease expression, in sheep with dual infection.
authors.affiliation: Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
authors.forename: J A
authors.initials: JA
authors.lastname: Ellis
authors.forename: H I
authors.initials: HI
authors.lastname: Russell
authors.forename: C W
authors.initials: CW
authors.lastname: Du
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015169:Colony Count, Microbial / Q000662:veterinary; D016925:Corynebacterium pseudotuberculosis / Q000254:growth & development / Q000502:physiology*; D016207:Cytokines / Q000494:pharmacology*; D017972:Lentiviruses, Ovine-Caprine / Q000254:growth & development / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000382:microbiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012756:Sheep; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D011994:Recombinant Proteins