1. ^*Departments of Industrial Hygiene and Toxicology and Occupational Medicine, the Finnish Institute of Occupational Health, Helsinki, Finland
2. ^†Department of Dermatology, University and University Hospital of Tampere, Tampere, Finland
3. ^‡Kymenlaakso Central Hospital, Kotka, Finland
4. ^§Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland
5. ^¶National Public Health Institute, Helsinki, Finland

Correspondence: Harri Alenius, PhD, Laboratory of Immunotoxicology, Finnish Institute of Occupational Health, Topeliuksenkatu 41 aA, FIN-00250 Helsinki, Finland. Email: harri.alenius@ttl.fi

Received 8 July 2002; Revised 8 October 2002; Accepted 11 November 2002.

Abstract

In addition to immediate type I allergy symptoms, natural rubber latex allergy may manifest as protein contact dermatitis on the hands of health-care workers and other natural rubber latex glove users. We examined whether repeated application of natural rubber latex on mouse skin causes sensitization to natural rubber latex and dermatitis. Epicutaneous sensitization with natural rubber latex produced a significant influx of mononuclear cells, CD4⁺ CD3⁺ cells, and eosinophils to the sensitized skin sites. The number of degranulated mast cells in natural rubber latex-sensitized skin sites was significantly higher compared with control sites treated with phosphate-buffered saline. The expression of interleukin-1 and interleukin-4 mRNA was markedly increased in natural rubber latex-sensitized skin sites. Moreover, significant increases in the mRNA expression of chemokines CCL2 (monocyte chemoattractant protein-1), CCL11 (eotaxin-1), CCL3 (macrophage inflammatory protein-1), and CCL4 (macrophage inflammatory protein-1) were found. In addition to the cutaneous inflammatory response, epicutaneous sensitization with natural rubber latex induced a striking increase in the total and specific immunoglobulin E levels but not in the immunoglobulin G2a levels. Intraperitoneal immunization with natural rubber latex induced a strong natural rubber latex-specific immunoglobulin G2a response, but only a weak immunoglobulin E response. We also studied the role of two major natural rubber latex allergens, the highly hydrophilic prohevein and the hydrophobic rubber elongation factor. Cutaneous application of natural rubber latex elicited a strong immunoglobulin E response against prohevein, but not against rubber elongation factor. On the contrary, intraperitoneal immunization with natural rubber latex elicited strong immunoglobulin G2a production to rubber elongation factor but not to prohevein. These results demonstrate that epicutaneous sensitization with natural rubber latex induces T helper 2-dominated dermal inflammation and strong immunoglobulin E response in this murine model of natural rubber latex induced protein contact dermatitis. Epicutaneous sensitization to natural rubber latex proteins eluting from latex gloves may therefore contribute to the development of hand dermatitis and also natural rubber latex-specific immunoglobulin E antibodies.