title: Effectiveness of a cytokine restraining agent (CRA (TM)) in attenuating disuse deconditioning induced by hindlimb unloading in rats.
abstract: Spaceflight alters many immune responses and among the regulatory components of an organisms response system that have been to be affected by spaceflight is the cytokine network.  Spaceflight, as well as ground-based model systems of spaceflight, have been shown to affect the production and activation of various cytokines including interleukins (IL) and tumor necrosis factor (TNF).  Levels of urinary IL-2 are elevated on the first day of spaceflight and again after returning from space.  Most results from ground-based studies in rodents indicate either no alterations in cytokines or decreased levels.  Results from this experiment indicate that HP 228, a potent cytokine restraining agent (CRA (TM)) was effective in attentuating many of the disuse deconditioning changes induced by the ground-based hindlimb suspension model that simulates weightlessness in rats.  HP 228 is a novel heptapeptide with unnatural amino acids and can effectively restrain lipopolysaccharide (LPS)-induced increased levels of several key cytokines, including plasma TNF alpha, IL-1 beta and IL-6.  HP 228 has also been shown to be effective in several rodent models of pain, inflammation and LPS-induced lethality, as well as in reducing inducible nitric oxide synthase.
authors.affiliation: Houghten Pharmaceuticals, Inc., San Diego, CA 92121, USA.
authors.forename: B
authors.initials: B
authors.lastname: Girten
authors.forename: S
authors.initials: S
authors.lastname: McPherson
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: N
authors.initials: N
authors.lastname: Grethe
authors.forename: R
authors.initials: R
authors.lastname: McDowell
authors.forename: L
authors.initials: L
authors.lastname: McPherson
authors.forename: R R
authors.initials: RR
authors.lastname: Tuttle
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D002950:Citrate (si)-Synthase / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects*; D004790:Enzyme Induction; D005080:Exercise Test; D006614:Hindlimb; D007103:Immobilization / Q000009:adverse effects*; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000378:metabolism; D018474:Weightlessness Simulation
chemical_list: D016207:Cytokines; D009842:Oligopeptides; C096756:HP 228; D002950:Citrate (si)-Synthase