Effect of IL-12 combined with soluble IL-4 receptor in thermally injured mice exposed to large amounts of herpes simplex virus type 1

R. B. Pollard, Makiko Kobayashi, David Herndon, Fujio Suzuki

Research output: Contribution to journalArticle

Abstract

Thermally injured mice, which mount Th2 responses, exhibit impaired resistance to infection with herpes simplex virus type 1 (HSV-1). Previously we reported that in thermally injured mice infected with HSV-1 at a dose of 5 LD50 (corresponds to 0.05 LD50 in normal mice), therapeutic treatment with IL-12 failed to inhibit the progression of the systemic disease. When EL-12 and soluble IL-4 receptor (sIL-4R) were administered together, they induced a marked recovery in the impaired resistance of thermally injured mice to HSV-1 infection. In the present study, therefore, the effect or a combination therapy between IL-12 and sIL-4R on a severe HSV-1 infection in thermally injured mice was investigated. BALB/c mice were exposed to a flame burn (3rd degree, 30% of total body surface area). Then, they were challenged i.p. with 50 to 500 LD50 of HSV-1 and treated with IL-12 and sIL-4R in combination. IL-12 was kindly provided by Hoffmann-La Roche, Inc., Nutley, NJ. Soluble IL-4 receptor (sIL-4R) was obtained commercially from Genzyme, Cambridge, MA. When thermally injured mice were treated with IL-12 (500 U/mouse, i.p, 2 and 4 days after thermal injury) or sDL-4R (50 μg/mouse, i.p., 1 and 4 days after thermal injury) alone, all of mice died within 13 days after the HSV-1 infection. However, 70% of HSV-1 infected thermally injured mice survived after the combination therapy between IL-12 and sH/-4R. At this time, 0% or 75% of normal mice treated with saline or IL-12 alone survived after the infection, respectively. These results suggest that the therapeutic IL-12 treatment combined with sIL-4R may result in the protection of thermally injured mice exposed to a severe HSV-1 infection.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

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Interleukin-4 Receptors
Human herpesvirus 1
interleukin-12
Human Herpesvirus 1
interleukin-4
Interleukin-12
Viruses
receptors
mice
Virus Diseases
Lethal Dose 50
lethal dose 50
heat injury
infection
therapeutics
Hot Temperature
Body Surface Area
Wounds and Injuries
Therapeutics
Recovery

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Effect of IL-12 combined with soluble IL-4 receptor in thermally injured mice exposed to large amounts of herpes simplex virus type 1. / Pollard, R. B.; Kobayashi, Makiko; Herndon, David; Suzuki, Fujio.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

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abstract = "Thermally injured mice, which mount Th2 responses, exhibit impaired resistance to infection with herpes simplex virus type 1 (HSV-1). Previously we reported that in thermally injured mice infected with HSV-1 at a dose of 5 LD50 (corresponds to 0.05 LD50 in normal mice), therapeutic treatment with IL-12 failed to inhibit the progression of the systemic disease. When EL-12 and soluble IL-4 receptor (sIL-4R) were administered together, they induced a marked recovery in the impaired resistance of thermally injured mice to HSV-1 infection. In the present study, therefore, the effect or a combination therapy between IL-12 and sIL-4R on a severe HSV-1 infection in thermally injured mice was investigated. BALB/c mice were exposed to a flame burn (3rd degree, 30{\%} of total body surface area). Then, they were challenged i.p. with 50 to 500 LD50 of HSV-1 and treated with IL-12 and sIL-4R in combination. IL-12 was kindly provided by Hoffmann-La Roche, Inc., Nutley, NJ. Soluble IL-4 receptor (sIL-4R) was obtained commercially from Genzyme, Cambridge, MA. When thermally injured mice were treated with IL-12 (500 U/mouse, i.p, 2 and 4 days after thermal injury) or sDL-4R (50 μg/mouse, i.p., 1 and 4 days after thermal injury) alone, all of mice died within 13 days after the HSV-1 infection. However, 70{\%} of HSV-1 infected thermally injured mice survived after the combination therapy between IL-12 and sH/-4R. At this time, 0{\%} or 75{\%} of normal mice treated with saline or IL-12 alone survived after the infection, respectively. These results suggest that the therapeutic IL-12 treatment combined with sIL-4R may result in the protection of thermally injured mice exposed to a severe HSV-1 infection.",
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