doi:10.1006/cyto.2001.0877, available online at http://www.idealibrary.com on INTERLEUKIN 1 COMPONENTS IN CICATRICIAL PEMPHIGOID. ROLE IN INTRAVENOUS IMMUNOGLOBULIN THERAPY Suman Kumari, 1 Kailash C. Bhol, 1 Farah Rehman, 1 C. Stephen Foster, 2 A. Razzaque Ahmed 1 Interleukin (IL-)1 is an important mediator of inflammatory responses and plays an important role in the pathogenesis of various autoimmune diseases. Cicatricial pemphigoid (CP) is a multisystem autoimmune inflammatory disease. We have studied the role of IL-1 in its pathogenesis. We have investigated the serum levels of IL-1 components (IL-1, IL-1, and IL-1Ra), and determined the role of intravenous immunoglobulin (IVIg) therapy in patients with CP. Serum levels of IL-1 and  were significantly higher in untreated patients with active disease compared to levels in patients in prolonged clinical remission and normal human controls (P<0.0001). The serum levels of IL-1Ra were higher in patients in prolonged clinical remission compared to patients with active disease (P =0.002). Hence elevated levels of IL-1 and  and low levels of IL-1Ra correlate with disease activity. The levels of IL-1 and  were statistically significantly higher in sera of CP patients with active disease pre-IVIg therapy compared to post-IVIg therapy (P<0.0001). Statistically significantly higher levels of IL-1Ra were present in post-IVIg treatment serum samples when compared to levels in pre-IVIg treatment (P<0.0001). In the in vitro experiments, the levels of IL-1 and  produced by the peripheral blood mononuclear cells (PBMC) isolated from patients before IVIg therapy were significantly higher when compared to the PBMC isolated from post-IVIg patients (P<0.0001). Significantly higher levels of IL-1Ra were observed in the supernatants of PBMC collected from pre-IVIg patients and cultured with exogenously added IVIg, when compared to the levels of PBMC to which IVIg was not added (P<0.0001). IL-1 may be an important cytokine involved in the pathogenesis of CP. The regulation of IL-1 could be one of the mechanisms, amongst others, by which IVIg may exert its beneficial effect in the treatment of CP.  2001 Academic Press Cicatricial pemphigoid (CP) is a multisystem autoimmune inflammatory disease that affects the con- junctiva and other mucous membranes containing stratified squamous epithelium and occasionally the skin. Progressive subepithelial fibrosis that accompa- nies the pathologic process of chronic conjunctivitis results in severe dryness of the eye, ocular keratiniza- tion and blindness secondary to corneal scarring. 1,2 The disease must be treated aggressively because of the potential for blindness. Dapsone is effective in approximately 70% of patients who have mild to moderate disease severity. For severe disease unrespon- sive to dapsone therapy, prednisone in combination with an immunosuppressive agent is often effective. 3 However some patients are refractory to such thera- pies. Intravenous immunoglobulin (IVIg) therapy has also been successfully used to treat such refractory CP patients. 4 High-dose IVIg therapy has been reported to be effective in treating many autoimmune diseases such as idiopathic thrombocytopenic purpura, systemic lupus erythematosus (SLE) and myasthenia gravis (MG). 5–8 However, the mechanism of action of IVIg therapy remains unclear. Its efficacy is thought to result from alterations in the IgG idiotype–anti-idiotypic network From the 1 Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, and Department of Medicine, New England Baptist Hospital, Boston, MA 02115; 2 Immunology and Uveitis Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA Correspondence to: A. Razzaque Ahmed, Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA. E-mail: razzaque_ahmed@hms.harvard.edu Received 29 December 2000; received in revised form 1 April 2001; accepted for publication 5 April 2001  2001 Academic Press 1043–4666/01/100218+07 $35.00/0 KEY WORDS: intravenous immunoglobulin/interleukin 1/ interleukin 1/interleukin 1 receptor antagonist/cicatricial pemphigoid CYTOKINE, Vol. 14, No. 4 (21 May), 2001: pp 218–224 218