Characteristics of IL‐6 and TNF‐α production by respiratory syncytial virus‐infected macrophages in the neonate

Abstract

The production of IL-6 and TNF-alpha and the expression of their mRNA were studied with neonatal (cord blood) and adult blood monocyte-derived macrophages (MDM) after in vitro infection with respiratory syncytial virus (RSV). Cord blood MDM exhibited production of high levels of IL-6 within 24 hr after infection. Little or no IL-6 production was detected after 24-48 hr and after in vitro stimulation with inactivated (nonreplicating) virus. Adult blood MDM also produced high levels of IL-6 within 24 hr of RSV infection. Unlike cord blood MDM, adult MDM demonstrated significant activity of IL-6 after 24 hr of infection with live RSV and after exposure to the inactivated virus. The pattern of TNF-alpha production by cord and adult blood MDM after live RSV infection resembled closely the pattern of IL-6 production. Both cell types produced TNF-alpha in the first 24 hr after infection. However, little or no production was observed after 24 hr of infection and after exposure to the inactivated virus. The profile of mRNA expression was similar to the production of IL-6 or TNF-alpha. mRNA expression occurred over a shorter period in cord blood MDM. These observations suggest that inflammatory and immunoregulatory cytokines, such as IL-6 and TNF-alpha, are produced by neonatal as well as previously primed adult macrophages. However, neonatal cells may be less efficient in inducing IL-6 production.

Differential expression of cytokine transcripts in neonatal and adult ovine alveolar macrophages in response to respiratory syncytial virus or toll-like receptor ligation

“…3A, B, and C). However, these responses in neonatal AM peaked early and were not sustained, similar to the previous report of Matsuda et al (1996) showing short-term expression of IL-6 or TNF-α in neonatal cord blood monocyte-derived macrophages. By comparison, a 1-4 fold increase in transcripts for IL-1β, IL-6 and IL-8 were observed in adult AMϕs.…”

“…We are aware of studies in which investigators compared neonatal and adult macrophage responses to RSV. However, in those studies, the authors utilized neonatal cord blood-derived and adult peripheral blood-derived Mϕs (Krishnan et al, 2003; Matsuda et al, 1996; Midulla et al, 1989). Midulla et al (2003) did examine alveolar macrophages in their study, but only isolated these cells from adult subjects.…”

Functionally Competent Eosinophils Differentiated Ex Vivo in High Purity from Normal Mouse Bone Marrow

“…Although eosinophils interact specifically with RSV (34), this is the first clear demonstration that pneumoviruses can infect and undergo replication within these cells. Likewise, although the nature of its role in the virus-induced inflammatory process is not clear, synthesis and secretion of IL-6 is a prominent response of respiratory epithelial cells and monocytes infected with RSV (35-39), and recently Lindemans and colleagues (40) detected IL-6 in culture supernatants from RSV-challenged human granulocytes. Interestingly, IL-6 has recently been implicated as a factor contributing to the severity of disease in respiratory distress – lung injury model in mice (41).…”

Cytokine and Chemokine Gene Expression after Primary and Secondary Respiratory Syncytial Virus Infection in Cotton Rats

“…IL-6 is expressed by RSV-infected lung epithelial cells [8] and monocytes [3,5,18], and its lack of expression in cotton rat secondary infection appears to be linked to the abortive cycle of viral replication. The induction of IFN-a expression by RSV has been controversial, with low or undetectable levels of IFN-a in nasal washes [19][20][21] or in peripheral blood monocytes and macrophages [22,23].…”