Management and Drug Therapy Int Arch Allergy Immunol 1995;107:321-322 Robert W . Egana Diljeet AthwahP Chuan-Chu Choua Spencer Emtageb Chung-Her Jehn a Ted T. Rung a Peter J. Mausera Nicholas J. Murgoloa Mark W . Bodmerb Inhibition of Pulmonary Eosinophilia and Hyperreactivity by Antibodies to lnterleukin-5 a Schering-Plough Research Institute, Kenilworth, N.J., USA; and b Celltech Research, Slough, Berkshire, UK Key Words Interleukin-5 Eosinophils Asthma Pulmonary inflammation Sch 55700 Abstract Eosinophils infiltrate into the lungs during asthma and may cause the damage associated with pulmonary inflammation. In allergic animal models, antibodies to interleukin (IL)-5 inhibit pulmonary eosinophilia, tissue damage and hyper reactivity. Sch 55700, a humanized antibody against human IL-5, inhibits eosi nophilia in these models with an extended biological duration. On the basis of this dosing regimen and the humanized nature of Sch 55700, it is anticipated that the host response leading to tolerance would be minimized. Eosinophils are a major cell type infiltrating into the lungs during asthma and have been implicated in the dam age associated with pulmonary inflammation [1], As one of their actions, steroids inhibit eosinophil infiltration, con tributing to their anti-inflammatory effects and their capac ity to enhance lung function in patients with asthma. How ever, steroids have side effects that limit their utility, and other approaches that selectivity block pulimonary eosino philia without causing generalized immunosuppression could lead to significant therapies for treating the causes of asthma. Interleukin (lL)-5 is a selective eosinophil effector in hu mans that enhances eosinophil production and release from bone marrow, chemotaxis, activation and survival [2], The neutralizing TRFK-5 antibody to IL-5 inhibits eosinophil infiltration into the lung tissue and lavage fluid following allergic challenge in sensitized guinea pigs, mice and mon keys [3, 4, 6J. Inhibition is observed when antibody is ad ministered intraperitoneally (i.p.), intravenously (i.v.) or in tramuscularly (i.m.) before or after the allergic challenge. In mice and probably in guinea pigs and monkeys, eosinophil accumulation in the lungs following antigen challenge is suppressed subsequent to inhibition of the release of eosi nophils from the bone marrow by the TRFK-5 antibody. De spite the multiplicity of cytokines involved in eosinophil production and activation, the TRFK-5 antibody can totally block eosinophil infiltration in these animal models, indi cating that these cytokines must act in series rather than in parallel and that IL-5 is involved in a terminal stage of eosi nophil maturation and release. The TRFK-5 antibody can also be administered during established eosinophilia, with out causing lung damage that could result from acute local degradation of eosinophils. Critical to any potential therapy for asthma is the capac ity to alter the physiology in these animal models. In the allergic guinea pig and monkey models, the animals’ lungs become hyperresponsive to substance P and histamine, re spectively, and this hyperresponsiveness is blocked by treat- Correspondence to: Dr. Robert W. ligan €> 1995 S. Karger AG, Basel Schering-Plough Research Institute 1018-2438/95/1073 0321 2015 Galloping Hill Road S8.00/0 Kenilworth. NJ 07033-0539 (USA)