Interleukin-1 Inhibitor Production by Human Mononuclear Leukocytes and Leukocyte Subpopulations Exposed to Respiratory Syncytial Virus: Analysis and Comparison With the Response to Influenza Virus

Abstract

Net interleukin-1 (IL-1) inhibitor activity is induced by exposure of purified human monocytes-macrophages to respiratory syncytial virus (RSV). Furthermore, IL-1 inhibitor activity was produced by monocytes-macrophages exposed to RSV in the presence of lymphocytes, that is, by unseparated mononuclear leukocytes (MNL). Purified RSV-exposed lymphocytes, as well as the lymphocytes exposed within MNL preparations, produced net IL-1 inhibitor activity. In contrast, net IL-1 activity was produced when purified monocytes-macrophages or unseparated MNL were exposed to influenza virus. The RSV-induced IL-1 inhibitors demonstrated antiproliferative effects on mitogen-stimulated human lymphocytes as well as on the mouse thymocytes used in standard assays. The results raise the possibility that such antiproliferative activity is mediated, at least in part, by monocytes-macrophages. The data also suggest that IL-1 inhibitors produced by MNL after exposure to RSV may contribute along with other factors to the recurrence of RSV infection in immune individuals.

Surfactant protein-A enhances respiratory syncytial virus clearance in vivo

“…TNF-α has been shown to have antiviral activity in vitro (40); however, in the present in vivo model, viral clearance was impaired in SP-A -/-mice despite increased TNF-α. RSV is known to be a poor inducer of IL-1 compared with viruses like parainfluenza and influenza (41). These data are consistent with the present study, demonstrating similar IL-1 levels in SP-A -/-and SP-A +/+ mice despite increased viral titers in SP-A -/-mice.…”

Alpha and Lambda Interferon Together Mediate Suppression of CD4 T Cells Induced by Respiratory Syncytial Virus

“…Figure 5 shows that there were no differences in supernatant derived from RSV-, UV-RSV-, or mock-exposed MDDC in concentrations of IL-1␣ or IL-1␤. Consistent with previous reports (32,46), IL-1RA levels were high in RSV supernatants and low in UV-RSV and mockinfected supernatants. Since we found very little IL-1␣ or -1␤, with no differences between the conditions and since the only known activity of IL-1RA is to block binding of IL-1␣/␤ to IL-1R, we did not explore further an immunosuppressive role for IL-1RA.…”

“…One such factor that has been held responsible for RSVinduced immunosuppression is IL-1RA (32,46). We found high levels of IL-1RA in the MDDC supernatants but very little IL-1␣ and IL-1␤, suggesting that IL-1RA probably has no role in this context.…”

“…Contact-dependent mechanisms (49), IL-1 receptor antagonist (IL-1RA) (32,46), and alpha inter-feron (IFN-␣) (42) have each been implicated but inconclusively so. The implication that IFN-␣ is immunosuppressive is somewhat paradoxical, since it is well documented that the nonstructural genes of RSV, NS1 and NS2, also decrease expression of the cellular responses to type I IFN (IFN-␣ and -␤) (47,48,58).…”

Tumour necrosis factor, IL-1 and IL-6 in bronchoalveolar washings and theirin vitroproduction duringNippostrongylus brasiliensisinfection

“…Additionally, as PMN are considered to be potent regulators ofthe immune responses [14], the increase in the percentage of neutrophils on days 2 and 3 post infection may explain Ihe fact that IL-I presence in BAW samples as well as TNF and lL-1 production by BAW-adherent cells in vitro, eeased after day I post infection. Il is also possible that the relaliveiy late production of lL-6 reguiates the production of the other cytokines [15] and that alveolar macrophages release inhibitory factors [16]. To exatnine this latter hypothesis, supernatants from BAW-adherent cells recovered on days 2 and 3 post infeclion were tested by the thymocyles proliferation assay for their ability to inhibit IL-I activity.…”