1282
The difference between Peters and colleagues’ experience and may have stemmed from their use of AL721 batches of incorrect composition or from their treatment of patients in a far more advanced stage of HIV infection. The ratio of the three components of AL721 must be correct for optimum activity.2We used a local product with confirmation of composition and activity. We also notedl that AL721 seemed to be of significant benefit at the less advanced stages of HIV infection; in most cases of AIDS this agent probably cannot cope. It has been postulated that AL721 acts on HIV in the serum and other interstitial fluids,3,4 while nucleotide analogues such as zidovudine block virus replication within infected cells. A combination of AL721 and zidovudine may be of therapeutic benefit and this is being tested in Europe. Our experience suggests that AL721, as a harmless antiviral lipid mixture, can be effective in treatment of symptom-free HIV disease or in prevention of HIV infection in high-risk populations. In more advanced infections it could act synergistically with nucleotide analogues. ours
Department of Membrane Research, Weizmann Institute of Science, 76100 Rehovot, Israel
MEIR SHINITZKY
Department of Surgery, Hospital, Tel-Aviv
YEHUDA SKORNICK
Ichilov
1. Yust I, Vardinon N, Skomick Y, Zakuth V, Hasner A, Shinitzky M. Reduction of circulating HIV antigens in seropositive patients after treatment with AL721. Israel J Med Sci 1990; 26: 20-26. 2. Lyte M, Shinitzky M. A special lipid mixture for membrane fluidization. Biochim Biophys Acta 1985; 812: 133-38. 3. Satin PS, Gallo RC, Scheer DI, Crews F, Lippa AS. Effects of a novel compound (AL721) on HTLV-1 infectivity in vitro. N Engl J Med 1985; 313: 1289-90. 4. Crews F, McElhaney B, Klepner C, Lippa AS. Lipids are major components of HIV: modification of HIV lipid composition, membrane organization and protein conformation by AL721. Drug Devel Res 1988; 14: 31-44.
followed by three injections per week for a further 3 weeks. After 2 weeks of therapy the inflammatory skin process had improved and after 4 weeks the eczema had nearly disappeared. In the 4 weeks after therapy there were no exacerbations. Moreover pruritus improved remarkably. Serum IgE levels gradually decreased during therapy and spontaneous IgE production in vitro was reduced (table). No significant changes in circulating T-cell subpopulations were observed during or after therapy. Our results provide striking evidence for the beneficial effects of recombinant IFN-y in subgroups of patients with atopic dermatitis and suggest the need for placebo-controlled studies.
Department of Dermatology, University of Bonn, D-5300 1, West Germany
UWE REINHOLD WOLFGANG WEHRMANN SYLVIA KUKEL HANS-WILHELM KREYSEL
G, Rousset F, de Vries JE. Alpha-interferon treatment of patient with hyper-IgE syndrome. Lancet 1989, ii’ 1384. 2. Reinhold U, Pawelec G, Wehrmann W, Herold M, Wemet P, Kreysel HW. Immunoglobulin E and immunoglobulin G subclass distribution in vivo and relationship to in vitro generation of interferon-gamma and neopterin in patients with severe atopic dermatitis. Int Arch Allergy Appl Immunol 1988; 87: 120-26. 3. Reinhold U, Wehrmann W, Kukel S, Kreysel HW. Evidence that defective interferon-gamma production in atopic dermatitis patients is due to intrinsic abnormalities. Clin Exp Immunol 1990; 79: 374-80. 4. Pene J, Rousset F, Briere F, et al. IgE production by normal human B cells induced by alloreactive T cell clones is mediated by IL-4 and suppressed by IFN-gamma. J Immunol 1988; 141: 1218-24. 5. Barker JNWN, MacDonald DM. Epidermal class II human lymphocyte antigen expression in atopic dermatitis: a comparison with experimental allergic contact Acad Dermatol 1988; 16: 1175-79. dermatitis. Am J 1. Souillet
Interferon-&agr; for atopic dermatitis Recombinant
interferon-&ggr; in severe atopic dermatitis
SiR,—Souillet et all reported that interferon-a (IFN-a) inhibited IgE synthesis in a patient with hyper-IgE syndrome. Serum IgE levels fell and the patient’s eczema improved. An antagonistic effect of IFN-a on interleukin-4-induced IgE production in vitro was suggested as a mode of action. We have reported that lymphocytes from patients with atopic dermatitis were profoundly defective in their capacity to secrete IFN-y, which was negatively correlated with serum IgE.2,3 Furthermore, skin-infiltrating lymphocytes isolated from lesions were defective in their capacity to secrete IFN-y but they produced high levels of interleukin-4 upon in-vitro stimulation (unpublished). It seemed possible that reduced IFN-y production enhances serum IgE concentrations in these patients.4 Moreover, defective IFN-y production of skin-infiltrating T-cells may contribute to observed defects in natural killer cell activity and enhanced susceptibility to viral skin infections and may be the reason why class II HLA antigens are not expressed on keratinocytes of inflammatory skin.5 These observations prompted us to treat three patients with recombinant IFN-y. The patients had unremitting severe atopic dermatitis and potent topical steroids had been unhelpful. They had high serum IgE concentrations, and spontaneous IgE production was high and IFN-y secretion defective in vitro. Subcutaneous injections of 100 pg IFN-y (specific activity 2-5 x 107 IU/mg; Bioferon Laupheim, West Germany) were given on 5 days of the first week of treatment, SERUM IgE AND IN-VITRO IgE PRODUCTION
*Spontaneous IgE production by 10. peripheral cultured in 10% fetal calf serum for 8 days
blood mononuclear cells/ml
SIR,-Reports of response to interferon (IFN) in patients with the hyper-IgE syndromel,2 prompted the suggestion that this agent might have a place in the treatment of severe allergy associated with very high serum IgE levels. Chronic atopic dermatitis is one such condition and it is much more common than hyper-IgE syndrome. We have given IFN-a unsuccessfully to two patients with intractable atopic dermatitis. Both were treated in winter because spontaneous improvement in atopic dermatitis is often seen in the spring and summer months. The first patient, a 24-year-old woman, has had severe atopic dermatitis with high serum concentrations of total IgE and IgE directed against house-dust mites and pollens. She has been admitted to hospital many times and requires continuous topical steroids. As an inpatient she was given three subcutaneous injections of IFN-a 106 units 48 h apart. When no side-effects were noted the dose was increased to 3 x 106 units thrice weekly and the patient was discharged, injections thereafter being given by the district nurse. Over 14 weeks she received 104 x 106 units. Eczema severity was monitored weekly by the Glasgow score which charts sixteen areas of the body on a severity scale of 0 to 3 for atopy, erythema, pustulation, excoriation, dryness, and cracking, for a maximum score of 240. Her eczema score fell from a baseline 72 to 48,51, and 54, but thereafter it rose slowly and was 112 when IFN-a was discontinued. Her total IgE at baseline was 17 U/ml with specific IgE levels to house-dust mite of 13and to grass pollens of 17-5 U/ml. These hardly altered and her use of topical steroids actually increased during the weeks of IFN administration. Natural killer (NK) cell activity is reduced in atopic eczema/,4so we monitored NK activity. Her NK cell activity was less than half that of age and sex matched controls and showed no significant variation throughout the study. No side-effects were observed and laboratory tests remained normal. The second patient, a 41-year-old woman with life-long atopic dermatitis also had severe atopic asthma requiring oral steroids. She was given the same regimen to a total IFN-a dose of 102 x 106 units over 12 weeks. No clinical improvement was observed and no significant changes in NK cell activity were noted. No abnormal laboratory tests were noted but small areas of alopecia areata did develop; she had no history of alopecia.
The difference between Peters and colleagues’ experience and may have stemmed from their use of AL721 batches of incorrect composition or from their treatment of patients in a far more advanced stage of HIV infection. The ratio of the three components of AL721 must be correct for optimum activity.2We used a local product with confirmation of composition and activity. We also notedl that AL721 seemed to be of significant benefit at the less advanced stages of HIV infection; in most cases of AIDS this agent probably cannot cope. It has been postulated that AL721 acts on HIV in the serum and other interstitial fluids,3,4 while nucleotide analogues such as zidovudine block virus replication within infected cells. A combination of AL721 and zidovudine may be of therapeutic benefit and this is being tested in Europe. Our experience suggests that AL721, as a harmless antiviral lipid mixture, can be effective in treatment of symptom-free HIV disease or in prevention of HIV infection in high-risk populations. In more advanced infections it could act synergistically with nucleotide analogues. ours
Department of Membrane Research, Weizmann Institute of Science, 76100 Rehovot, Israel
MEIR SHINITZKY
Department of Surgery, Hospital, Tel-Aviv
YEHUDA SKORNICK
Ichilov
1. Yust I, Vardinon N, Skomick Y, Zakuth V, Hasner A, Shinitzky M. Reduction of circulating HIV antigens in seropositive patients after treatment with AL721. Israel J Med Sci 1990; 26: 20-26. 2. Lyte M, Shinitzky M. A special lipid mixture for membrane fluidization. Biochim Biophys Acta 1985; 812: 133-38. 3. Satin PS, Gallo RC, Scheer DI, Crews F, Lippa AS. Effects of a novel compound (AL721) on HTLV-1 infectivity in vitro. N Engl J Med 1985; 313: 1289-90. 4. Crews F, McElhaney B, Klepner C, Lippa AS. Lipids are major components of HIV: modification of HIV lipid composition, membrane organization and protein conformation by AL721. Drug Devel Res 1988; 14: 31-44.
followed by three injections per week for a further 3 weeks. After 2 weeks of therapy the inflammatory skin process had improved and after 4 weeks the eczema had nearly disappeared. In the 4 weeks after therapy there were no exacerbations. Moreover pruritus improved remarkably. Serum IgE levels gradually decreased during therapy and spontaneous IgE production in vitro was reduced (table). No significant changes in circulating T-cell subpopulations were observed during or after therapy. Our results provide striking evidence for the beneficial effects of recombinant IFN-y in subgroups of patients with atopic dermatitis and suggest the need for placebo-controlled studies.
Department of Dermatology, University of Bonn, D-5300 1, West Germany
UWE REINHOLD WOLFGANG WEHRMANN SYLVIA KUKEL HANS-WILHELM KREYSEL
G, Rousset F, de Vries JE. Alpha-interferon treatment of patient with hyper-IgE syndrome. Lancet 1989, ii’ 1384. 2. Reinhold U, Pawelec G, Wehrmann W, Herold M, Wemet P, Kreysel HW. Immunoglobulin E and immunoglobulin G subclass distribution in vivo and relationship to in vitro generation of interferon-gamma and neopterin in patients with severe atopic dermatitis. Int Arch Allergy Appl Immunol 1988; 87: 120-26. 3. Reinhold U, Wehrmann W, Kukel S, Kreysel HW. Evidence that defective interferon-gamma production in atopic dermatitis patients is due to intrinsic abnormalities. Clin Exp Immunol 1990; 79: 374-80. 4. Pene J, Rousset F, Briere F, et al. IgE production by normal human B cells induced by alloreactive T cell clones is mediated by IL-4 and suppressed by IFN-gamma. J Immunol 1988; 141: 1218-24. 5. Barker JNWN, MacDonald DM. Epidermal class II human lymphocyte antigen expression in atopic dermatitis: a comparison with experimental allergic contact Acad Dermatol 1988; 16: 1175-79. dermatitis. Am J 1. Souillet
Interferon-&agr; for atopic dermatitis Recombinant
interferon-&ggr; in severe atopic dermatitis
SiR,—Souillet et all reported that interferon-a (IFN-a) inhibited IgE synthesis in a patient with hyper-IgE syndrome. Serum IgE levels fell and the patient’s eczema improved. An antagonistic effect of IFN-a on interleukin-4-induced IgE production in vitro was suggested as a mode of action. We have reported that lymphocytes from patients with atopic dermatitis were profoundly defective in their capacity to secrete IFN-y, which was negatively correlated with serum IgE.2,3 Furthermore, skin-infiltrating lymphocytes isolated from lesions were defective in their capacity to secrete IFN-y but they produced high levels of interleukin-4 upon in-vitro stimulation (unpublished). It seemed possible that reduced IFN-y production enhances serum IgE concentrations in these patients.4 Moreover, defective IFN-y production of skin-infiltrating T-cells may contribute to observed defects in natural killer cell activity and enhanced susceptibility to viral skin infections and may be the reason why class II HLA antigens are not expressed on keratinocytes of inflammatory skin.5 These observations prompted us to treat three patients with recombinant IFN-y. The patients had unremitting severe atopic dermatitis and potent topical steroids had been unhelpful. They had high serum IgE concentrations, and spontaneous IgE production was high and IFN-y secretion defective in vitro. Subcutaneous injections of 100 pg IFN-y (specific activity 2-5 x 107 IU/mg; Bioferon Laupheim, West Germany) were given on 5 days of the first week of treatment, SERUM IgE AND IN-VITRO IgE PRODUCTION
*Spontaneous IgE production by 10. peripheral cultured in 10% fetal calf serum for 8 days
blood mononuclear cells/ml
SIR,-Reports of response to interferon (IFN) in patients with the hyper-IgE syndromel,2 prompted the suggestion that this agent might have a place in the treatment of severe allergy associated with very high serum IgE levels. Chronic atopic dermatitis is one such condition and it is much more common than hyper-IgE syndrome. We have given IFN-a unsuccessfully to two patients with intractable atopic dermatitis. Both were treated in winter because spontaneous improvement in atopic dermatitis is often seen in the spring and summer months. The first patient, a 24-year-old woman, has had severe atopic dermatitis with high serum concentrations of total IgE and IgE directed against house-dust mites and pollens. She has been admitted to hospital many times and requires continuous topical steroids. As an inpatient she was given three subcutaneous injections of IFN-a 106 units 48 h apart. When no side-effects were noted the dose was increased to 3 x 106 units thrice weekly and the patient was discharged, injections thereafter being given by the district nurse. Over 14 weeks she received 104 x 106 units. Eczema severity was monitored weekly by the Glasgow score which charts sixteen areas of the body on a severity scale of 0 to 3 for atopy, erythema, pustulation, excoriation, dryness, and cracking, for a maximum score of 240. Her eczema score fell from a baseline 72 to 48,51, and 54, but thereafter it rose slowly and was 112 when IFN-a was discontinued. Her total IgE at baseline was 17 U/ml with specific IgE levels to house-dust mite of 13and to grass pollens of 17-5 U/ml. These hardly altered and her use of topical steroids actually increased during the weeks of IFN administration. Natural killer (NK) cell activity is reduced in atopic eczema/,4so we monitored NK activity. Her NK cell activity was less than half that of age and sex matched controls and showed no significant variation throughout the study. No side-effects were observed and laboratory tests remained normal. The second patient, a 41-year-old woman with life-long atopic dermatitis also had severe atopic asthma requiring oral steroids. She was given the same regimen to a total IFN-a dose of 102 x 106 units over 12 weeks. No clinical improvement was observed and no significant changes in NK cell activity were noted. No abnormal laboratory tests were noted but small areas of alopecia areata did develop; she had no history of alopecia.
