Negative regulatory effect of histamine in DNFB-induced contact hypersensitivity

Abstract

Histamine plays an important role in the regulation of various immunological functions. To evaluate the role of histamine in contact hypersensitivity, contact dermatitis was induced with dinitrofluorobenzene (DNFB) in histidine decarboxylase knockout (HDC-/-) histamine-deficient and wild-type mice. The DNFB-induced increase of the ear thickness was significantly higher in HDC-/- mice than in wild-type mice. Using flow cytometry, significantly lower percentages of CD4+ Th and CD8+ Tc cells, and significantly higher percentages of CD45R+ B cells were observed in the regional lymph nodes in HDC-/- mice than in wild-type mice. In the ear specimens of both groups, the majority of the infiltrating cells were neutrophils and macrophages at 24 and 48 h after challenge. Using immunohistochemistry, we observed significantly more CD45+ leukocytes in HDC-/- mice than in wild-type mice. The expression of Th1 (IL-2, IFN-gamma, TNF-alpha) and Th2 (IL-4) mRNAs was examined by quantitative real time RT-PCR in the ear samples. The levels of Th1 cytokine mRNAs both at 24 and 48 h after challenge and IL-4 mRNA at 48 h showed a significantly higher increase in HDC-/- mice than in wild-type mice. These results suggest that histamine plays a negative immunoregulatory role in DNFB-induced contact hypersensitivity.

A Key Regulatory Role for Histamine in Experimental Autoimmune Encephalomyelitis: Disease Exacerbation in Histidine Decarboxylase-Deficient Mice

“…Because it is difficult to achieve complete and long-lasting elimination of the effects of histamine in vivo using pharmacological approaches (32), HDC Ϫ/Ϫ mice provide a good model in which to study autoimmune responses against CNS myelin in the virtual absence of any kind of regulation mediated by histamine. Of note, histamine can be ingested by HDC Ϫ/Ϫ mice through the diet; nevertheless, these mice have been kept under a normal diet in several previous studies (38,46,54,55,(57)(58)(59). We analyzed the histamine content of several tissues of HDC Ϫ/Ϫ mice and clearly showed that under a normal diet these mice are still profoundly histamine deficient compared to the wild-type mice.…”

Analysis of Histamine Receptor Knockout Mice in Models of Inflammation

“…Thus, in these models, neutrophil-derived histamine may serve as an autocrine factor that reduces or delays neutrophil inflammation; however, this has not been formally proven so far. Despite its reported anti-inflammatory role in contact dermatitis (Garaczi et al, 2004), histamine seems to mediate scratching behavior in diphenylcyclopropenoneinduced contact dermatitis. Scratching activity was dramatically reduced in HDC-deficient mice compared with wild-type controls .…”

“…In contrast to the observed proinflammatory role of histamine are results of studies in models of acute contact dermatitis (Garaczi et al, 2004) and experimentally induced peritonitis (Hori et al, 2002). In these models, histamine deficiency accelerates neutrophil and macrophage accumulation into dermis and peritoneum, respectively, indicating an antiinflammatory effect of histamine, which can be attributed to the functional expression of H 2 R in these cells (Hasturk et al, 2006;Cho et al, 2011;Reher et al, 2012a).…”

Inhibition of Delayed-Type Hypersensitivity by Cucurbitacin R through the Curbing of Lymphocyte Proliferation and Cytokine Expression by Means of Nuclear Factor AT Translocation to the Nucleus

“…The elicitation phase occurs after further contact with the hapten, giving rise to the recruitment of antigen-specific T cells and resulting in severe dermal inflammation (Scott et al, 2002). This in turn leads to the release of different mediators such as interferon-␥, tumor necrosis factor (TNF)-␣, interleukin (IL)-2, IL-4, and IL-10 by T lymphocytes; IL-12 and IL-18 by Langerhans cells (Garaczi et al, 2004); nitric oxide by keratinocytes and Langerhans cells (Ross and Reske-Kunz, 2001); and IL-1␤ (Zunic et al, 1998), leukotrienes, and prostaglandins by macrophages (Meurer et al, 1988). In contrast, the DTH induced by SRBC is an immunological reaction mediated by specific, committed T cells.…”