Allergic and autoimmune reactions to xenobiotics: how do they arise?

Griem, Peter; Wulferink, Marty; Sachs, Bernhardt; González, J. Sanz; Gleichmann, Ernst

doi:10.1016/s0167-5699(98)80012-1

Cited by 175 publications

(59 citation statements)

References 67 publications

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“…Release of DNA from the apoptotic cells has been proposed as the source of antigenic DNA for anti-DNA antibody synthesis in this model (30,31,52). Others have proposed that apoptotic cells provide autoantigens as well (73,74 (76). Urushiol, the irritant in poison ivy, is a linically relevant example of this (76).…”

Section: Signaling Modifiersmentioning

confidence: 95%

“…Others have proposed that apoptotic cells provide autoantigens as well (73,74 (76). Urushiol, the irritant in poison ivy, is a linically relevant example of this (76). Once a response is initiated, the phenomenon of epitope spreading may occur, in which antigenic epitopes associated with but physically distinct from the hapten are progressively recognized by responding T and B cells (77).…”

Section: Signaling Modifiersmentioning

confidence: 99%

“…Heavy metals have been implicated in triggering some forms of autoimmunity (76). Heavy metal ions of mercury, gold, and nickel will bind proteins, altering molecular and antigenic properties.…”

Section: Signaling Modifiersmentioning

confidence: 99%

“…Gold salts are implicated in autoimmune thrombocytopenia and immune complex glomerulonephritis through unknown mechanisms (76 …”

Section: Cryptic Epitopesmentioning

confidence: 99%

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Environmentally induced autoimmune diseases: potential mechanisms.

Rao

Richardson

1999

Environ Health Perspect

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Environmental and other xenobiotic agents can cause autoimmunity. Examples include drug-induced lupus, toxic oil syndrome, and contaminated l-tryptophan ingestion. Numerous mechanisms, based on (italic)in vitro(/italic) evidence and animal models, have been proposed to explain how xenobiotics induce or accelerate autoimmunity. The majority of these can be divided into three general categories. The first is those inhibiting the processes involved in establishing tolerance by deletion. Inhibiting deletion can result in the release of newly generated autoreactive cells into the periphery. The second mechanism is the modification of gene expression in the cells participating in the immune response, permitting lymphocytes to respond to signals normally insufficient to initiate a response or allowing the antigen-presenting cells to abnormally stimulate a response. Abnormal gene expression can thus disrupt tolerance maintained by suppression or anergy, permitting activation of autoreactive cells. The third is the modification of self-molecules such that they are recognized by the immune system as foreign. Examples illustrating these concepts are presented, and related mechanisms that have the potential to similarly affect the immune system are noted. Some mechanisms appear to be common to a variety of agents, and different mechanisms appear to produce similar diseases. However, evidence that any of these mechanisms are actually responsible for xenobiotic-induced human autoimmune disease is still largely lacking, and the potential for numerous and as yet unidentified mechanisms also exists.

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Section: Signaling Modifiersmentioning

confidence: 95%

Section: Signaling Modifiersmentioning

confidence: 99%

Section: Signaling Modifiersmentioning

confidence: 99%

“…Gold salts are implicated in autoimmune thrombocytopenia and immune complex glomerulonephritis through unknown mechanisms (76 …”

Section: Cryptic Epitopesmentioning

confidence: 99%

See 2 more Smart Citations

Environmentally induced autoimmune diseases: potential mechanisms.

Rao

Richardson

1999

Environ Health Perspect

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“…However, the most widely accepted view is that covalent modi®cation leads to perturbation of the host's own immune system. Following antigen recognition, the drug-modi®ed protein is processed and presented in association with MHC class I and/or II molecules to T-cells (signal 1) (Coleman & Blanca, 1998;Griem et al, 1998). Signal 1 governs the nature of the immune response (i.e., CD4 + or CD8 + ) (Kalish & Askenase, 1999), while co-stimulatory signals (signal 2) and/or cytokine synthesis (signal 3) determine whether antigen presentation results in tissue damage or tolerance (Curtsinger et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Antigenicity and immunogenicity of sulphamethoxazole: demonstration of metabolism‐dependent haptenation and T‐cell proliferation in vivo

Naisbitt

Gordon

Pirmohamed

et al. 2001

British J Pharmacology

124

116

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1 Sulphamethoxazole has been associated with the occurrence of hypersensitivity reactions. There is controversy as to whether the immune response is metabolism-dependent or -independent. We have therefore investigated the site of antigen formation and the nature of the drug signal presented to the immune system in vivo. 2 Male Wistar rats were dosed with sulphamethoxazole, sulphamethoxazole hydroxylamine or nitroso sulphamethoxazole. Antigen formation on cell surfaces was determined by¯ow cytometry using a speci®c anti-sulphamethoxazole antibody. Immunogenicity was determined by assessment of ex vivo T-cell proliferation. 3 Administration of nitroso sulphamethoxazole, but not sulphamethoxazole or sulphamethoxazole hydroxylamine, resulted in antigen formation on the surface of lymphocytes, splenocytes and epidermal keratinocytes, and a strong proliferative response of splenocytes on re-stimulation with nitroso sulphamethoxazole. Rats dosed with sulphamethoxazole or sulphamethoxazole hydroxylamine did not respond to any of the test compounds. 4 CD4 + or CD8 + depleted cells responded equally to nitroso sulphamethoxazole. The proliferative response to nitroso sulphamethoxazole was seen even after pulsing for only 5 min, and was not inhibited by glutathione. Responding cells produced IFN-g, but not IL-4. 5 Haptenation of cells by sulphamethoxazole hydroxylamine was seen after depletion of glutathione by pre-treating the rats with diethyl maleate. Splenocytes from the glutathione-depleted sulphamethoxazole hydroxylamine-treated rats responded weakly to nitroso sulphamethoxazole, but not to sulphamethoxazole or sulphamethoxazole hydroxylamine. 6 Dosing of rats with sulphamethoxazole produced a cellular response to nitroso sulphamethoxazole (but not to sulphamethoxazole or its hydroxylamine) when the animals were primed with complete Freund's adjuvant. 7 These studies demonstrate the antigenicity of nitroso sulphamethoxazole in vivo and provide evidence for the role of drug metabolism and cell surface haptenation in the induction of a cellular immune response in the rat.

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Increased production of interferon-gamma, but not IL-4 mRNA, by streptozotocin in the popliteal lymph node assay

et al. 2000

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The popliteal lymph node (PLN) assay has been proposed as a tool to predict systemic autoimmune reactions induced by medicinal products and chemicals, the mechanisms of which are poorly understood. To determine whether PLN responses involved Th1 or Th2 cell control, or both, the effects of streptozotocin (STZ), a prototypic immunotoxic compound, were analysed on the production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) mRNA by lymph node cells after injection into the hind footpad of C57 BL/6 mice. Streptozotocin induced a dramatic increase in IFN-gamma mRNA production, which correlated with PLN responses as evidenced by augmented weight and cellularity indices. No effect on IL-4 mRNA synthesis was noted. These results suggest that a Th1 response is involved in the PLN response to STZ.

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Allergic and autoimmune reactions to xenobiotics: how do they arise?

Cited by 175 publications

References 67 publications

Environmentally induced autoimmune diseases: potential mechanisms.

Environmentally induced autoimmune diseases: potential mechanisms.

Antigenicity and immunogenicity of sulphamethoxazole: demonstration of metabolism‐dependent haptenation and T‐cell proliferation in vivo

Increased production of interferon-gamma, but not IL-4 mRNA, by streptozotocin in the popliteal lymph node assay

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