Immunocytochemical localization of inducible nitric oxide synthase and transforming growth factor-beta (TGF-β) in leprosy lesions

Khanolkar-Young, S.; Snowdon, Diane; Lockwood, Diana N J

doi:10.1046/j.1365-2249.1998.00669.x

Cited by 36 publications

(38 citation statements)

References 18 publications

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“…However, several studies have shown that iNOS is expressed, as detected by immunohistochemistry, at the site of disease in patients infected with intracellular pathogens, including M. leprae. Khanolkar-Young et al (210), using antibodies against iNOS, found that iNOS was highly expressed in the lesions of tuberculoid leprosy patients and was increased to even higher levels during the reversal reaction (see below). Moreover, the levels of iNOS subsided over the course of prednisolone treatment (233).…”

Section: (Iii) Cytotoxic Cells (A) T Cells Cd8mentioning

confidence: 99%

The Continuing Challenges of Leprosy

et al. 2006

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SUMMARY Leprosy is best understood as two conjoined diseases. The first is a chronic mycobacterial infection that elicits an extraordinary range of cellular immune responses in humans. The second is a peripheral neuropathy that is initiated by the infection and the accompanying immunological events. The infection is curable but not preventable, and leprosy remains a major global health problem, especially in the developing world, publicity to the contrary notwithstanding. Mycobacterium leprae remains noncultivable, and for over a century leprosy has presented major challenges in the fields of microbiology, pathology, immunology, and genetics; it continues to do so today. This review focuses on recent advances in our understanding of M. leprae and the host response to it, especially concerning molecular identification of M. leprae, knowledge of its genome, transcriptome, and proteome, its mechanisms of microbial resistance, and recognition of strains by variable-number tandem repeat analysis. Advances in experimental models include studies in gene knockout mice and the development of molecular techniques to explore the armadillo model. In clinical studies, notable progress has been made concerning the immunology and immunopathology of leprosy, the genetics of human resistance, mechanisms of nerve injury, and chemotherapy. In nearly all of these areas, however, leprosy remains poorly understood compared to other major bacterial diseases.

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Section: (Iii) Cytotoxic Cells (A) T Cells Cd8mentioning

confidence: 99%

The Continuing Challenges of Leprosy

et al. 2006

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“…Hence, down-regulation of TNF-␣ could be crucial for reducing inflammation during reactions. Expression of tumor necrosis factor ␤1 (TGF-␤1), an important regulator of inflammation and wound healing, is decreased in skin in T1R (18), and thus up-regulation of TGF-␤1 could be beneficial for resolution of the reaction.…”

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confidence: 99%

Effects of Prednisolone Treatment on Cytokine Expression in Patients with Leprosy Type 1 Reactions

et al. 2005

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Leprosy type 1 reactions (T1R) are due to increased cell-mediated immunity and result in localized tissue damage. The anti-inflammatory drug prednisolone is used for treatment, but there is little good in vivo data on the molecular actions of prednisolone. We investigated the effect of prednisolone treatment on tumor necrosis factor alpha (TNF-␣), interleukin-1␤ (IL-1␤), IL-10, and transforming growth factor ␤1 (TGF-␤1) mRNA and protein expression in blood and skin biopsies from 30 patients with T1R in India. After 1 month of prednisolone treatment the sizes of the skin granulomas were reduced, as were the grades of cells positive for TNF-␣ and IL-10 in skin lesions. Increased production of TGF-␤1 was seen in skin lesions after 6 months of prednisolone treatment. Expression of mRNA for TNF-␣, IL-1␤, and TGF-␤1 was reduced, whereas no change in IL-10 mRNA expression was detected during treatment. The circulating cytokine profiles were similar in patients with and without T1R, and prednisolone treatment had no detectable effects on cytokine expression in the blood. The data emphasize the compartmentalization of pathology in T1R and the importance of the immune response in the skin. Clinical improvement and cytokine expression were compared. Surprisingly, patients with improved skin and nerve function and patients with nonimproved skin and nerve function had similar cytokine profiles, suggesting that clinical improvement is not directly mediated by the cytokines studied here. This in vivo well-controlled study of the immunosuppressive effects of prednisolone showed that the drug does not switch off cytokine responses effectively.

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“…There is an influx of CD4 ϩ cells into lesions (10), and elevated levels of cytokine mRNA and protein have been detected in situ, including IFN-␥, IL-1␤, IL-2, IL-12, and tumor necrosis factor ␣ (4, 7, 14-16). Furthermore, increased levels of the enzymeinducible nitric oxide synthase (iNOS) are found in reactional lesions (8), indicating an enhanced intracellular killing capacity of macrophages. Reactions are painful and frequently result in significant nerve damage.…”

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confidence: 99%

Immunohistochemical Analysis of Cellular Infiltrate and Gamma Interferon, Interleukin-12, and Inducible Nitric Oxide Synthase Expression in Leprosy Type 1 (Reversal) Reactions before and during Prednisolone Treatment

et al. 2001

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The effects of prednisolone treatment on the cellularity and cytokine (gamma interferon, interleukin-12, and inducible nitric oxide synthase) profiles of leprosy skin type 1 (reversal) reactions were studied using immunohistochemistry. Skin biopsies were taken from 15 patients with leprosy type 1 (reversal) reactions at days 0, 7, 28, and 180 after the start of steroid treatment. Prednisolone treatment had little effect at day 7, but by day 28 significant decreases were found in cytokine levels. Some patients maintained cytokine production at days 28 and 180. These results illustrate the strong Th1 profile of type 1 reactional lesions, the slow response to steroid therapy, and continuing activity at 180 days.

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Immunocytochemical localization of inducible nitric oxide synthase and transforming growth factor-beta (TGF-β) in leprosy lesions

Cited by 36 publications

References 18 publications

The Continuing Challenges of Leprosy

The Continuing Challenges of Leprosy

Effects of Prednisolone Treatment on Cytokine Expression in Patients with Leprosy Type 1 Reactions

Immunohistochemical Analysis of Cellular Infiltrate and Gamma Interferon, Interleukin-12, and Inducible Nitric Oxide Synthase Expression in Leprosy Type 1 (Reversal) Reactions before and during Prednisolone Treatment

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