Teresa Y. Basham

Regulation of expression of class II major histocompatibility antigens on human peripheral blood monocytes and langerhans cells by interferon

Although normal peripheral blood monocytes from different individuals are primarily DR+ (L243), they vary in the mean expression of L243 and the percentage of cells with detectable Leu-10 (DC/DS) and L03 (D). All three species of human recombinant IFNs enhance Ia expression on normal peripheral blood monocytes; however, r-IFN-gamma is much more effective in enhancing the expression of these three class II antigens in vitro than r-IFN-beta or r-IFN-alpha A. In addition, r-IFN-gamma has a more profound effect on the expression of Leu-10 (DC/DS), an antigen critical for presentation in autologous MLR, than on L243 (DR). Adherent monocytes cultured for 5 days develop macrophage characteristics and become strongly positive for all three of these class II antigens without further manipulation. Isolated skin Langerhans cells which are thought to be antigen presenting cells in the epidermis are also strongly positive for all three of these Ia antigens and are unaffected by IFN treatment. Therefore, this early interferon effect on cell surface expression may be the result of enhancing the maturation of monocytes to mature antigen presenting cells.

Keratinocyte class II histocompatibility antigen expression

SIR, Etretinate has been attributed with several side-effects, none of which are life threatening (Michaelsson er a/., i98i;Foged&Jacobsen, 1982; Lauharanta, i982;Fontan,Benafe&Moatti, 1983). We should like to report a serious side-effect caused by therapeutic doses of etretinate (Tigason®, Roche). A 27-year-old woman with no knovvTi allergies and longstanding, widespread, plaque psoriasis had been treated with limited success with topical therapy. She had normal renal and hepatic function with a raised mean corpuscular volume (MCV) of 106 fl (cause unknown). She was started on an oral regimen of etretinate (25 mg per day: approximately 05 mg/kg/day). Eight days later she developed a severe pruritus with marked swelling and exfoliation of her limbs. Within a further 24 hours she became erythrodermic with severe exhaustion and raised temperature. Two days after the appearance of these symptoms she stopped taking the etretinate, and presented at the casualty department as an emergency. On admission the patient was ill, febrile (38°C) and erythrodermic, with peripheral and facial oedema, mild groin lymphadenopathy and tender hepatomegaly. The serum albumin was low at 24 g/1. The MCV was raised to ioi fl. The patient recovered over 10 days using a regime of albumin infusion, temperature control and topical steroids. Two hours following a challenge oral dose of etretinate the patient once again developed the symptoms and signs described above. It seems likely that etretinate was responsible for this reaction. The low serum albumin may have contributed to a rise in the proportion of free drug (DeWitt & Goodman, 1982) and toxic levels may have been reached with therapeutic doses of this compound. Despite the severity of the reaction the patient recovered completely with therapy and drug withdrawal. In view of the increasing use of etretinate the possibility of serious side-effects should be considered and patients closely monitored during therapy.

Interferon enhances antibody-dependent cellular cytotoxicity when suboptimal concentrations of antibody are used

Polymorphonuclear leukocytes (PMN) and killer (K) cells isolated from buffy coats from normal volunteers were tested for antibody-dependent cellular cytotoxicity (ADCC) against chicken erythrocytes (CRBC) with and without the addition of interferon (IFN). Maximum enhancing activity was found when the anti-CRBC antibodies in the ADCC reaction were at suboptimal concentrations. All three species of pure recombinant Escherichia coli-derived interferon were compared for their ability to enhance ADCC in both effector systems. Recombinant IFN-gamma was found to be effective at lower doses than recombinant IFN-alpha A or recombinant IFN-beta, although maximum activity for all three species was similar in the PMN system. IFN-gamma also enhanced K-cell ADCC but to a lesser extent than in the PMN system. There appeared to be individual variation in response of the K-cell ADCC system to IFN-alpha A and IFN-beta at the doses tested.