A pathogenic role of IL-12 in blood-stage murine malaria lethal strain Plasmodium berghei NK65 infection

Takayuki Yoshimoto, Yasuhiro Takahama, Chrong Reen Wang, Toshihiko Yoneto, Seiji Waki, Hideo Nariuchi

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Abstract

We studied whether the infection with a blood-stage murine malaria lethal Plasmodium berghei NK65 induces IL-12 production, and if so, how the IL-12 production is involved in the protection or pathogenesis. The infection of C57BL/6 mice enhanced mRNA expression of IL-12 p40 and also IFN-γ, IL-4, and IL-10 in both spleen and liver during the early course of the infection. It also enhanced the mRNA expression of TNF-α, Fas ligand, and cytokine- inducible nitric oxide synthase. Increased IL-12 p40 production was also observed in the culture supernatant of spleen cells and in sera of infected mice. In addition, the infection caused massive liver injury with elevated serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase activities and body weight loss. Treatment of these infected mice with neutralizing mAb against IL-12 prolonged the survival and diminished the liver injury with reduced elevation of serum serum glutamic- oxaloacetic transaminase and serum glutamic-pyruvic transaminase activities and decreased body weight loss. However, the anti-IL-12 treatment did not affect parasitemia, and all these mice eventually died. Similar results were obtained when infected mice were treated with neutralizing mAb against IFN- γ. Moreover, anti-IL-12 treatment greatly reduced the secretion and mRNA expression of IFN-γ in both spleen and liver. These results suggest that the lethal P. berghei NK65 infection induces IL-12 production and that the IL-12 is involved in the pathogenesis of liver injury via IFN-γ production rather than the protection.

Original languageEnglish
Pages (from-to)5500-5505
Number of pages6
JournalJournal of Immunology
Volume160
Issue number11
Publication statusPublished - 1998 Jun 1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Yoshimoto, T., Takahama, Y., Wang, C. R., Yoneto, T., Waki, S., & Nariuchi, H. (1998). A pathogenic role of IL-12 in blood-stage murine malaria lethal strain Plasmodium berghei NK65 infection. Journal of Immunology, 160(11), 5500-5505.