The role of endogenous interleukin-12 in resistance to murine cytomegalovirus (MCMV) infection and a novel action for endogenous IL-12 p40

J A Carr, J A Rogerson, M J Mulqueen, N A Roberts, A A Nash

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Biologically active interleukin-12 (IL-12), comprising a 40 kDa subunit (p40) covalently linked to a 35 kDa subunit (p35), is produced in response to a range of infectious stimuli. Here, we demonstrate that mice deficient in either IL-12 p40 (p40-/-) or IL-12 p35 (p35-/-) are susceptible to murine cytomegalovirus (MCMV) infection in terms of survival (Balb/c p35-/-) and viral clearance (Balb/c p35-/- and Balb/c p40-/-), and this susceptibility may be correlated to a deficiency in serum interferon-gamma (IFN-gamma) levels. These data support a role for endogenous IL-12 in controlling MCMV infection. The IL-12 p40 subunit is produced in excess of IL-12 p35, and to date the function of the excess endogenous p40 has been assumed to be one of IL-12 antagonism, as demonstrated by experiments with exogenous p40 both in vivo and in vitro. We show that Balb/c p35-/- alone are significantly compromised in survival of a sublethal infection and in clearance of virus from the spleen. These mice produce a very early IFN-gamma spike (8 h after infection) and an aberrant tumor necrosis factor-alpha (TNF-alpha) spike (day 2 after infection). MCMV infection has revealed an altered Balb/c p35-/- phenotype compared with Balb/c p40-/-, and this indicates that endogenous p40 may have an activity independent of and additional to IL-12 antagonism in vivo.
Original languageEnglish
Pages (from-to)1145-52
Number of pages8
JournalJournal of Interferon and Cytokine Research
Volume19
Issue number10
DOIs
Publication statusPublished - Oct 1999

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Cytomegalovirus Infections
  • Immunity, Innate
  • Interleukin-12
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred BALB C
  • Peptide Fragments
  • Survival Rate
  • Up-Regulation

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