stinguish responders from nonresponders, resulting in a dichotomous categorization of clinical asthma into a disease with evidence of predominant type-2 inflammation or a disease with min1 Conflict of interest: All authors are or were employed by Genentech Inc. at the time of the study and hold equity in the Roche Group. In addition, the research in this manuscript was fully funded by Genentech Inc. Submitted: January PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19837474 25, 2016 Accepted: April 12, 2016 Published: May 19, 2016 Systemic lupus erythematosus, a disease of unknown etiology that is more common in women than in men, is characterized by nondestructive arthritis/arthralgias, a cutaneous rash, vasculitis, involvement of the central nervous system, and renal and cardiopulmonary manifestations. Although genetic, environmental, and sex hormonal factors have been implicated in the pathogenesis of SLE, it is known that several cytokines, nitric oxide, free radicals, a deranged immune system, deficient antioxidant defenses, and toll-like receptors have a significant role both in the initiation and perpetuation of the inflammatory process observed. The fundamental process in lupus appears to be rendering DNA and RNA antigenic, which leads to the production of anti-DNA and 
anti-RNA antibodies and the formation of Journal of Inflammation Research 2010:3 143170 2010 Das, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Correspondence: Undurti N Das UND Life Sciences, 13800 Fairhill Road, #321, Shaker Heights, OH 44120, USA Tel +1 216 231 5548 Fax +1 928 833 0316 email [email protected] Dovepress DOI: 10.2147/JIR.S9425 143 Das Dovepress immune complexes. These antibodies and immune complexes in turn trigger both a local and systemic inflammatory response that ultimately leads to target organ/tissue GW 501516 chemical information damage seen in lupus. The susceptibility for a given individual to develop lupus seems to have, at least partly, a genetic basis, though this is still not very clear. Once the inflammatory process is triggered, this leads to the production of a variety of proinflammatory cytokines such as interleukin -1, IL-6, tumor necrosis factor-, interferons, macrophage migration inhibitory factor, HMGB-1, and possibly a reduction in the elaboration of anti-inflammatory cytokines such as IL-10, IL-4, and transforming growth factor-. This imbalance between the pro- and anti-inflammatory cytokines coupled with increased secretion of free radicals such as superoxide anion, hydrogen peroxide, singlet oxygen, inducible nitric oxide, and other reactive oxygen species by activated monocytes, macrophages, polymorphonuclear leukocytes, T-cells, Kupffer cells, glial cells in the brain, and other organ-specific reticuloendothelial cells would ultimately cause target tissue/organ damage seen in lupus. No lupus patients have the same manifestations, and the clinical presentation of the same patient at different time periods could be variable. For example, initially, a particular patient may present with cutaneous manifestations and over a period of time might L-arginine Inflammatory stimulus eNOS/nNOS iNOS PMN, macrophages, endothelial cells Activation of NADPH oxidase MPO NO +CL- HOCL develop involvement of joints, kidneys, and other organs. Similarly, the response of patients with lupus and rheumatoid arthritis is variable. Some respond, others may not respond, and some show only partial response to
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