49 results about "Interleukin 1 β" patented technology

The present invention relates to novel classes of compounds which are inhibitors of interleukin-1β converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against interleukin-1 mediated diseases, including inflammatory diseases, autoimmune diseases and neurodegenerative diseases. This invention also relates to methods for inhibiting ICE activity and methods for treating interleukin-1 mediated diseases using the compounds and compositions of this invention.

This invention is directed to a method of using a therapeutic composition comprising a compound of an alpha-ketoalkanoic acid (pyruvate) and/or its derivatives for the treatment of cytokine-mediated inflammatory conditions. The compound is an alpha-ketoalkanoic acid, a physiologically acceptable salt of an alpha-ketoalkanoic acid, an ester of an alpha-ketoalkanoic acid, or an amide of an alpha-ketoalkanoic acid. A component for inducing and stabilizing the enol resonance form of the ester at physiological pH values is also disclosed. The cytokine-mediated inflammatory conditions are mediated by, for example, an “early” (Tumor Necrosis Factor (TNF), interleukin-1β (IL-1β)) or “late” (high mobility group B-1 (HMGB-1)) mediator of inflammation. Exemplary cytokine-mediated inflammatory conditions include, but are not limited to, local and systemic inflammation, inflammatory bowel disease (Crohn's disease and ulcerative colitis), rheumatoid arthritis, asthma (including status asthmaticus), sepsis or septic shock, also including inflammatory skin conditions, for example, psoriasis and eczema.

A method of modulating topical inflammatory response is disclosed. The method generally includes the selective removal of certain proteins, e.g., one or more cytokines such as interleukin-1β (IL-1β) and/or interleukin-6 (IL-6), from a topical site without substantially altering the local concentrations of other proteins that may be present at or near the topical site. Other proteins that are present at or near the topical site can include serum albumin, fibrinogen, and immunoglobin G (IgG). Hydrogel compositions that can be used to practice the methods of the invention are provided. The invention further provides methods of preparing such hydrogel compositions.

The invention discloses an efficient CIK amplifying method, in particular to a method for cell populations, namely cytokine-induced killer cells utilizing in-vitro cell factors for efficiently inducing mononuclear cell expressions CD3 and CD56 of peripheral blood, wherein the cell populations have killing functions. The cultivation method for the CIK efficiently expressing CD3+CD56 comprises the following steps that the peripheral blood of a healthy person or a patient is collected in a sterile mode, after the peripheral blood is diluted through a saline solution with the same volume, a Ficoll lymphocyte separating medium is used for separating mononuclear cells, in the CIK cell inducing process, CD3 monoclonal antibodies (CD3mAb), CD28 monoclonal antibodies (CD28mAb), interferon-gamma (IFN-gamma), interleukin-2(IL-2) and interleukin 1alpha (IL-1alpha) are added, cultivation is carried out for 13-16 days to obtain cells, a CIK cell preparation is prepared, and flow cytometry detection and microorganism detection are carried out. According to the CIK cultivation method, the CIK number can be increased to be 6*10<9> or over 6*10<9> in two weeks, the cell survival rate can be increased to be 99% or over 99%, and the double-positive proportion of the CD3+CD56+cells reaches 30% or over 30%.

Human α-defensins are inhibitors of interleukin-1β post transitional processing and release. Interleukin-1β is a key cytokine involved in the initiation and amplification of the inflammatory process, including the inflammation of diseases such as Crohn's Disease and Ulcerative Colitis. Particularly, human neutrophil defensin-1(HNP-1) produced mainly by neutrophils, and human α-defensin 5(HD-5) produced by Paneth cells has been found to block interleukin-1β post transitional processing and release. Thus, a pharmaceutical composition and method for treating inflammation in the mammalian tissues is herein disclosed. The pharmaceutical composition is a therapeutic supplementation of a metabolic pathway to reduce inflammation comprising a human α-defensins in a therapeutically effective amount or an amide, ester or salt thereof and a pharmaceutically effective carrier. The method for treating inflammation in mammalian tissues includes administering a human α-defensins to a mammal in an amount effective to inhibit the post translational processing and release of interleukin-1β.

There is disclosed an isolated polypeptide and derivatives thereof having protease biological activity for human precursor IL-1β and for a substrate comprising:

R₁—Asp—R₂—R₃

wherein R₁ and R₃ are independently any D or L isomer amino acid, R₂ is Ala or Gly, and wherein the specific protease cleavage site is between Asp and R₂. Inhibitor compounds, compositions and methods for inhibiting Interleukin 1β protease activity are also disclosed. The inhibitor compounds comprise an amino acid sequence of from 1 to about 5 amino acids having an N-terminal blocking group and a C-terminal Asp residue connected to an electronegative leaving group, wherein the amino acid sequence corresponds to the sequence Ala-Tyr-Val-His-Asp.

The present invention relates to methods and compositions for diagnosis of inflammatory disorders, and in non-limiting embodiments, of inflammatory disorders associated with elevated interleukin-1β (“IL-1β”), based on increased levels of follistatin-like protein 1 (“FSTL-1”). In particular non-limiting embodiments, the invention further provides for methods of identifying subjects with systemic onset juvenile idiopathic arthritis (“SOJIA”) who are at increased risk for developing macrophage activation syndrome (“MAS”) comprising detecting, in said subjects, hyper-increased levels of FSTL-1. In additional non-limiting embodiments, the invention provides for methods of identifying subjects with Kawasaki disease who are at increased risk of developing aortic aneurysms comprising detecting, in said subjects, hyper-increased levels of FSTL-1.

A method of diagnosing or determining the degree of an arterial aneurysm, especially an abdominal aortic aneurysm, which comprises determining the presence or level of interleukin-1α (IL-1aα) in a serum or plasma sample.

A method of diagnosing or determining the degree of an arterial aneurysm, especially an abdominal aortic aneurysm, which comprises determining the presence or level of interleukin-1α (IL-1α) in a serum or plasma sample.

We provide monoclonal antibodies against interleukin-1β and tumor necrosis factor-α that remain biologically active in vitro when conjugated to high molecular weight polysaccharides. We report enhanced binding of these cytokines when their monoclonal antibodies are conjugated to alginate compared to non-conjugated monoclonal antibodies. In cell assays, polysaccharide-antibody constructs of the invention inhibited cytokine signaling to comparable levels as that of unmodified antibodies. Conjugation of cytokine-neutralizing antibodies to high molecular weight polymers enhances the affinities cytokine-binding moieties used as anti-inflammatory therapeutics.