Cytokine production during murine cytomegalovirus infection

Elizabeth Fitzpatrick, S. Humphries, W. Gatterdam, C. Pomeroy

Research output: Contribution to journalArticle

Abstract

Cytomegalovirus (CMV) is a major cause of morbidity and mortality among immunocompromised patients and improved therapies are urgently needed. Manipulation of cytokines represents a potential immunomodulatory approach to treatment of CMV infection. To define cytokine responses during CMV infection, we studied serum cytokine concentrations in succeptible Balb/c mice and relatively resistant C57BL/6 mice after injection with murine CMV (MCMV). Serum interferon-γ (IFN-γ) levels peak at Day 2 in resistant C57BL/6 mice, but IFN-γ responses are delayed in susceptible Balb/c mice with peaks occuring at Day 6-7. IL-12 is detected in the serum of both Balb/c and C57BL/6 mice by Day 2, suggesting that the delay in IFN-γ production in Balb/c mice is not due to delayed or defective IL-12 signaling. Pro-inflammatory cytokines including TNF-α, IL-1, and IL-6 are produced early after MCMV infection with peak serum levels appearing by Day 2 in both groups of mice. IL-10 levels peak later in the course of MCMV infection, after serum concentrations of the proinflammatory cytokines begin to decrease. IL-2 (reflecting Th-1) and IL-4 (reflecting Th-2) type cytokines are not detected. Serum TGF-β levels decrease from baseline levels in both Balb/c and C57BL/6 mice, with nadir levels observed on Day 3-4, corresponding to peaks of the proinflammatory cytokines. In summary, macrophage derived cytokines, including IL-12, are produced early in MCMV infection in both Balb/c and C57BL/6 mice. Strain differences in susceptibility to MCMV may be attributable to differential IFN-γ production. Th-1 and Th-2 type cytokines do not appear to play a major role in the response to MCMV. We conclude that MCMV infection is accompanied by a characteristic pattern of cytokine responses. These observations provide a basis for the development of potential immunomodulatory therapies which may eventually prove useful for treatment of human CMV disease.

Original languageEnglish (US)
Number of pages1
JournalClinical Infectious Diseases
Volume25
Issue number2
StatePublished - Dec 1 1997
Externally publishedYes

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Muromegalovirus
Cytomegalovirus Infections
Cytokines
Inbred C57BL Mouse
Interferons
Interleukin-12
Serum
Infection
Cytomegalovirus
Immunomodulation
Immunocompromised Host
Interleukin-1
Interleukin-4
Interleukin-10
Interleukin-2
Interleukin-6
Therapeutics
Macrophages

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Cytokine production during murine cytomegalovirus infection. / Fitzpatrick, Elizabeth; Humphries, S.; Gatterdam, W.; Pomeroy, C.

In: Clinical Infectious Diseases, Vol. 25, No. 2, 01.12.1997.

Research output: Contribution to journalArticle

Fitzpatrick, E, Humphries, S, Gatterdam, W & Pomeroy, C 1997, 'Cytokine production during murine cytomegalovirus infection', Clinical Infectious Diseases, vol. 25, no. 2.
Fitzpatrick, Elizabeth ; Humphries, S. ; Gatterdam, W. ; Pomeroy, C. / Cytokine production during murine cytomegalovirus infection. In: Clinical Infectious Diseases. 1997 ; Vol. 25, No. 2.
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