Abstract: In various embodiments, the present invention is drawn to antibodies or antigen-binding fragments thereof that bind to particular fragments of HMGB1, methods of treating a condition in a subject characterized by activation of an inflammatory cytokine cascade, methods of detecting and/or identifying an agent that binds to an HMGB1 polypeptide or fragment thereof, and methods of detecting HMGB1 in a sample.

Abstract: Methods are disclosed for treating sepsis and septic shock using a combination of ghrelin and growth hormone, and for using ghrelin to reduce organ and tissue injury and improve survival after combined radiation exposure and sepsis.

Abstract: The present invention provides methods of treating inflammatory diseases in a subject comprising administering to the subject a therapeutically effective amount of an agent that inhibits pigment epithelium-derived factor (PEDF) and methods of screening for agents that inhibit PEDF.

Abstract: Described herein are methods, devices and systems for inhibition of granulocyte activation by appropriate stimulation of the vagus nerve. Methods of treating granulocyte-mediated disorders (including inflammatory disorders) by stimulating the vagus nerve to inhibit granulocyte activation (particularly neutrophil activation) are also described. Appropriate stimulation may be very low levels of stimulation, including stimulation that does not result in desensitization. The level of granulocyte activation may be detected and used to at least partially control stimulation.

Abstract: There is disclosed a pharmaceutical composition and method for treating sepsis, including septic shock and ARDS (acute respiratory distress syndrome), comprising administering an effective amount of a HMG1 antagonist. There is further disclosed a diagnostic method for monitoring the severity or potential lethality of sepsis or septic shock, comprising measuring the serum concentration of HMG1 in a patient exhibiting or at risk of exhibiting sepsis or septic shock symptoms. Lastly, there is disclosed a phamaceutical composition and method for effecting weight loss or treating obesity, comprising administering an effective amount of HMG1 or a therapeutically active HMG1 fragment.

Abstract: Provided are various compounds of Formula I (I). Also provided are various compounds of Formula II (II). Also provided are pharmaceutical compositions comprising the above compounds. Additionally, methods of inhibiting macrophage migration inhibitory factor (MIF) activity in a mammal are provided, as are methods of treating or preventing inflammation in a mammal. Further provided are methods of treating a mammal having sepsis, septicemia, and/or endotoxic shock. Also provided are methods of treating a mammal having an autoimmune disease, and methods of treating a mammal having a tumor.

Abstract: In various embodiments, the present invention is drawn to antibodies or antigen-binding fragments thereof that bind to particular fragments of HMGB1, methods of treating a condition in a subject characterized by activation of an inflammatory cytokine cascade, methods of detecting and/or identifying an agent that binds to an HMGB1 polypeptide or fragment thereof, and methods of detecting HMGB1 in a sample.

Abstract: A method of treating a fatty liver disease in a subject. The method comprises administering to the subject an effective amount of a cholinergic pathway stimulating agent, wherein the fatty liver disease is selected from non-alcoholic fatty liver (NAFL), alcoholic fatty liver (AFL), non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), NASH-associated liver fibrosis, ASH-associated liver fibrosis, non-alcoholic cirrhosis, and alcoholic cirrhosis.

Abstract: Methods are disclosed for treating sepsis and septic shock using a combination of ghrelin and growth hormone, and for using ghrelin to reduce organ and tissue injury and improve survival after combined radiation exposure and sepsis.

Abstract: The present invention is directed to a method of treating a subject at risk for or having a condition mediated by an inflammatory cytokine cascade comprising administering to the subject an amount of a GAPDH inhibitor effective to treat the subject at risk for or having a condition mediated by an inflammatory cytokine cascade.

Abstract: Provided are various compounds of Formula (I): Also provided are pharmaceutical compositions comprising the above compounds. Additionally, methods of inhibiting macrophage migration inhibitory factor (MIF) activity in a mammal are provided, as are methods of treating or preventing inflammation in a mammal. Further provided are methods of treating a mammal having sepsis, septicemia, and/or endotoxic shock. Also provided are methods of treating a mammal having an autoimmune disease, and methods of treating a mammal having a tumor.

Abstract: The invention features a method of treating an inflammatory condition in an individual, comprising administering an agent inhibits the interaction between a Toll-like receptor 2 (TLR2) and a high mobility group B (HMGB) polypeptide to the individual. The invention also features methods for identifying agents that inhibit the interaction between TLR2 and HMGB.

Abstract: The present invention provides a method for treating a subject having chronic lymphocytic leukemia (CLL) comprising administering to the subject one or more agents that target cell surface membrane antigens expressed preferentially on cells of the proliferative compartment of a CLL clone of the subject to treat chronic lymphocytic leukemia in the subject. The present invention also provides a method for treating a subject having chronic lymphocytic leukemia comprising administering to the subject one or more agents that target cell surface membrane antigens expressed preferentially on cells of the “resting re-entry compartment” to treat chronic lymphocytic leukemia in the subject.

Abstract: There is disclosed a pharmaceutical composition and method for treating sepsis, including septic shock and ARDS (acute respiratory distress syndrome), comprising administering an effective amount of a HMG1 antagonist. There is further disclosed a diagnostic method for monitoring the severity or potential lethality of sepsis or septic shock, comprising measuring the serum concentration of HMG1 in a patient exhibiting or at risk of exhibiting sepsis or septic shock symptoms. Lastly, there is disclosed a pharmaceutical composition and method for effecting weight loss or treating obesity, comprising administering an effective amount of HMG1 or a therapeutically active HMG1 fragment.

Abstract: Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise, for example, high affinity antibodies that specifically bind HMG1 and antigenic fragments thereof. The high affinity antibodies of the present invention and pharmaceutical compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of inflammatory diseases and disorders such as sepsis, rheumatoid arthritis, peritonitis, Crohn's disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, psoriasis, psoriatic arthritis, arthritis, anaphylactic shock, organ ischemia, reperfusion injury, and allograft rejection. In addition, the high affinity antibodies of the present inventions are useful as diagnostic antibodies.

Abstract: Provided are isolated and purified preparations of a combination of a light chain antibody gene and a heavy chain antibody gene, where the light chain and heavy chain antibody genes are the same among more than one patient with B cell chronic lymphocytic leukemia (B-CLL). Vectors comprising those genes and cells comprising those vectors are also provided, as are isolated and purified antibodies encoded by the antibody genes. Anti-idiotype antibodies, peptides, and aptamers that bind to the antigen-binding region of an antibody encoded by the antibody genes are additionally provided, as are multimeric molecules comprising multiple binding sites that bind to the antigen-binding region of an antibody encoded by the antibody genes.

Abstract: Provided are peptides having melanocyte stimulating hormone activity. Also provided are vectors encoding these peptides and transgenic cells comprising the above vectors. Additionally, methods of reducing or preventing release of an inflammatory cytokine from mammalian cells are provided, as are methods for treating a mammal suffering from, or at risk for, a condition mediated by an inflammatory cytokine cascade. Further provided are methods of reducing levels of an inflammatory cytokine in a mammal, methods of treating an overweight mammal, methods of decreasing food intake in a mammal and methods of inhibiting innate immunity in the digestive system of a mammal.

Abstract: There is disclosed a pharmaceutical composition and method for treating sepsis, including septic shock and ARDS (acute respiratory distress syndrome), comprising administering an effective amount of a HMG1 antagonist. There is further disclosed a diagnostic method for monitoring the severity or potential lethality of sepsis or septic shock, comprising measuring the serum concentration of HMG1 in a patient exhibiting or at risk or exhibit sepsis or septic shock symptoms. Lastly, there is disclosed a pharmaceutical composition and method for effecting weight loss or treating obesity, comprising administering an effective amount of HMG1 or a therapeutically active HMG1 fragment.

Abstract: Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise a vertebrate HMGB A box, and an antibody preparation that specifically binds to a vertebrate HMGB B box. The methods comprise treating a cell or a patient with sufficient amounts of the composition to inhibit the release of the proinflammatory cytokine, or to inhibit the inflammatory cytokine cascade.

Abstract: Methods of inhibiting release of a proinflammatory cytokine from a macrophage are provided. The methods comprise treating the macrophage with a cholinergic agonist in an amount sufficient to decrease the amount of the proinflammatory cytokine that is released from the macrophage, wherein the cholinergic agonist is selective for an ?7 nicotinic receptor. Methods for inhibiting an inflammatory cytokine cascade in a patient are also provided. The methods comprise treating the patient with a cholinergic agonist in an amount sufficient to inhibit the inflammatory cytokine cascade, wherein the cholinergic agonist is selective for an ?7 nicotinic receptor. Methods for determining whether a compound is a cholinergic agonist reactive with an ?7 nicotinic receptor are also provided. The methods comprise determining whether the compound inhibits release of a proinflammatory cytokine from a mammalian cell.