Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions

Katsunori Sugisaki, Arthur M. Dannenberg, Yasuharu Abe, Junji Tsuruta, Wei Juin Su, Waheeda Said, Lili Feng, Teizo Yoshimura, Paul J. Converse, Phoebe Mounts

Research output: Contribution to journalArticle

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Abstract

To our knowledge, this is the first sequential study of cytokines in tissue sections of developing and healing tuberculous (BCG) lesions. In situ hybridization, immunohistochemical, and RT-PCR techniques were used. Cytokine mRNAs showed a biphasic pattern. The percentage of mononuclear cells (MN) containing IL-1β, TNF-α, MCP-1, and IL-8 mRNAs was highest in 1- to 3-day lesions, apparently because of the nonspecific inflammatory response caused by the tubercle bacilli in the BCG vaccine. At 5 days, this percentage was significantly reduced. With IFN-γ, the peak and trough were delayed by 2 days. By 9 days, the percentage of MN containing the mRNAs of all five cytokines had again increased and the rabbits had become tuberculin-positive. In general, MCP-1 and TNF-α proteins and the vascular adhesion molecules, ICAM, VCAM, and perhaps ELAM, peaked at about 3 days. Many mononuclear cells surrounding the central areas of solid and liquefied caseous necrosis contained chemokine IL-8 mRNA. IL-8 is known to attract PMN, and PMN were present nearby. In contrast, MN containing chemokine MCP-1 mRNA were present more peripherally in areas rich in macrophages and lymphocytes. The early nonspecific cytokine response seems to be an adjuvant effect of the mycobacteria in BCG vaccine in that it causes a rapid entry of macrophages, lymphocytes, granulocytes, and probably dendritic cells into local sites of antigen deposition. This effect should be considered in developing improved vaccines for the prevention of tuberculosis, because BCG vaccines producing a strong early cytokine response should be more immunogenic than BCG vaccines with similar antigens producing a weak response.

Original languageEnglish
Pages (from-to)440-450
Number of pages11
JournalJournal of Leukocyte Biology
Volume63
Issue number4
Publication statusPublished - Apr 1998
Externally publishedYes

Fingerprint

BCG Vaccine
Mycobacterium bovis
Up-Regulation
Cytokines
Rabbits
Messenger RNA
Skin
Interleukin-8
Chemokines
Macrophages
Tuberculosis Vaccines
Lymphocytes
Antigens
Tuberculin
Mycobacterium
Interleukin-1
Granulocytes
Dendritic Cells
Bacillus
In Situ Hybridization

Keywords

  • ELAM-1 (E- selectin)
  • IFN-γ ICAM-1
  • IL-1β
  • IL-8 (NAP-1)
  • MCP-1
  • TNF-α
  • VCAM-1

ASJC Scopus subject areas

  • Cell Biology

Cite this

Sugisaki, K., Dannenberg, A. M., Abe, Y., Tsuruta, J., Su, W. J., Said, W., ... Mounts, P. (1998). Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions. Journal of Leukocyte Biology, 63(4), 440-450.

Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions. / Sugisaki, Katsunori; Dannenberg, Arthur M.; Abe, Yasuharu; Tsuruta, Junji; Su, Wei Juin; Said, Waheeda; Feng, Lili; Yoshimura, Teizo; Converse, Paul J.; Mounts, Phoebe.

In: Journal of Leukocyte Biology, Vol. 63, No. 4, 04.1998, p. 440-450.

Research output: Contribution to journalArticle

Sugisaki, K, Dannenberg, AM, Abe, Y, Tsuruta, J, Su, WJ, Said, W, Feng, L, Yoshimura, T, Converse, PJ & Mounts, P 1998, 'Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions', Journal of Leukocyte Biology, vol. 63, no. 4, pp. 440-450.
Sugisaki K, Dannenberg AM, Abe Y, Tsuruta J, Su WJ, Said W et al. Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions. Journal of Leukocyte Biology. 1998 Apr;63(4):440-450.
Sugisaki, Katsunori ; Dannenberg, Arthur M. ; Abe, Yasuharu ; Tsuruta, Junji ; Su, Wei Juin ; Said, Waheeda ; Feng, Lili ; Yoshimura, Teizo ; Converse, Paul J. ; Mounts, Phoebe. / Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions. In: Journal of Leukocyte Biology. 1998 ; Vol. 63, No. 4. pp. 440-450.
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