RPEP-00033 · 1985Thymosin alpha 1 (Ta-1) had strikingly different effects depending on the mouse strain. In B10.D2 mice (resistant to autoimmune thyroiditis), Ta-1 treatment between the two antigen injections actually increased thyroid inflammation. In B10.Br mice (naturally susceptible), Ta-1 suppressed the disease.
Timing mattered. Early treatment (first 2 weeks) suppressed disease in the susceptible strain but worsened it in the resistant strain. Later treatment (weeks 3-4) had similar patterns.
Different doses affected different T-cell subsets. The 0.01 microgram dose lowered Lyt-2+3+ cells (a type of immune cell) in resistant mice. The 0.001 microgram dose raised Lyt-1+ cells in the same strain. Each dose shifted the immune balance differently, which explains the opposing disease outcomes.
Tomazic, V J; Novotny, E A; Ordonez, J V · Animal Study
RPEP-00081 · 1988Within 24 hours of inflammation, dynorphin increased specifically in the ipsilateral (same-side) dorsal horn of the spinal cord. Met-enkephalin, leu-enkephalin, and opioid receptor densities did not change.
The inflamed paw showed pronounced supersensitivity to morphine's painkilling effect against pressure pain, starting at 24 hours and increasing at 1 week.
Opioid antagonists (naloxone and the kappa-preferring MR 2266) made the pain worse, suggesting endogenous opioids were already partially controlling the pain.
By 3-5 weeks, inflammation had spread to the opposite paw. Dynorphin was now elevated bilaterally and in the cervico-thoracic cord. Met-enkephalin and leu-enkephalin also rose bilaterally. Adrenal glands were enlarged and plasma beta-endorphin was elevated, signs of chronic stress.
No changes in mu, delta, or kappa receptor density were found at any time point.
Millan, M J; Członkowski, A; Morris, B; Stein, C; Arendt, R; Huber, A; Höllt, V; Herz, A · Animal Study
RPEP-00165 · 1990Morphine has anti-inflammatory effects on granulocytes through both opioid receptor-dependent (aggregation, ATP) and independent (arachidonic acid metabolism) mechanisms. Natural opioid peptides do not share these effects.
Mazzone, A; Ricevuti, G; Pasotti, D; Fioravanti, A; Marcoli, M; Lecchini, S; Notario, A; Frigo, G M · In Vitro
RPEP-00172 · 1990Immune cells in inflamed tissue release opioid peptides that activate receptors on sensory nerve terminals, producing local pain relief. This represents a newly discovered neuroimmune analgesic pathway.
Stein, C; Hassan, A H; Przewłocki, R; Gramsch, C; Peter, K; Herz, A · Animal Study
RPEP-00191 · 1991Chronic constriction injury and inflammation both upregulated spinal preprodynorphin mRNA rapidly and sustainably. Complete nerve transection and crush did not.
Draisci, G; Kajander, K C; Dubner, R; Bennett, G J; Iadarola, M J · Animal Study
RPEP-00193 · 1991VIP is diminished in intestinal smooth muscle of Crohn's patients. Substance P receptors are markedly increased at small vessels and lymph nodules in inflamed IBD intestine.
Eysselein, V E; Nast, C C · Review
RPEP-00212 · 1991Chronic inflammation increased basal enkephalin release but abolished CRF-stimulated release of all three opioid peptides from the hypothalamus. KCl-stimulated release remained intact.
Shippenberg, T S; Herz, A; Nikolarakis, K · Animal Study
RPEP-00225 · 1992Central TNF-alpha and IL-1-alpha both increased nociceptive thresholds. TNF-alpha decreased locomotion. Naloxone partially reversed TNF-alpha's analgesic effect.
Bianchi, M; Sacerdote, P; Ricciardi-Castagnoli, P; Mantegazza, P; Panerai, A E · Animal Study
RPEP-00236 · 1992Dynorphin immunoreactivity detected in both inflammatory cells and cutaneous sensory nerve fibers in Freund's adjuvant-inflamed rat paw tissue.
Hassan, A H; Pzewłocki, R; Herz, A; Stein, C · Animal Study
RPEP-00245 · 1992Intrathecal mu and delta agonists produced enhanced antinociception in monoarthritic rats with greater cAMP inhibition. Kappa agonists showed no enhancement.
Przewłocka, B; Dziedzicka, M; Lasoń, W; Przewłocki, R · Animal Study
RPEP-00246 · 1992All three opioid precursor mRNAs detected in inflamed tissue. Opioid peptides localized to immune cells. Local opioid blockade increased pain, proving functional significance.
Przewłocki, R; Hassan, A H; Lason, W; Epplen, C; Herz, A; Stein, C · Animal Study
RPEP-00250 · 1992Native opioid peptides did not affect PMN respiratory burst. Opioid peptides modified by activated oxygen species enhanced PMA-stimulated respiratory burst.
Slaoui-Hasnaoui, A; Guerin, M C; Le Doucen, C; Loubatiere, J; Torreilles, J · In Vitro
RPEP-00279 · 1993BPC 157 from gastric juice shows broad organoprotection across multiple stress models. The stomach may initiate a body-wide protective response during stress via peptide mediators.
Sikirić, P; Petek, M; Rucman, R; Seiwerth, S; Grabarević, Z; Rotkvić, I; Turković, B; Jagić, V; Mildner, B; Duvnjak, M · Review
RPEP-00280 · 1993All three opioid peptides found in synovial immune cells. Intra-articular naloxone increased post-surgical knee pain, proving endogenous opioids provide functional local analgesia.
Stein, C; Hassan, A H; Lehrberger, K; Giefing, J; Yassouridis, A · Cross Sectional
RPEP-00307 · 1994IL-1 beta and CRF caused immune cells in inflamed tissue to release opioid peptides that produced local pain relief, blocked by naloxone and anti-opioid antibodies.
Schäfer, M; Carter, L; Stein, C · Animal Study
RPEP-00309 · 1994BPC 157 was the only tested compound that consistently protected against gastric and duodenal ulcers in all three models, regardless of whether given before, during, or after ulcer induction.
Sikiric, P; Seiwerth, S; Grabarevic, Z; Petek, M; Rucman, R; Turkovic, B; Rotkvic, I; Jagic, V; Duvnjak, M; Mise, S · Animal Study
RPEP-00323 · 1995Dynorphin A dose-dependently enhanced macrophage phagocytosis through a naloxone-insensitive (non-opioid receptor) mechanism.
Ichinose, M; Asai, M; Sawada, M · In Vitro
RPEP-00383 · 1996BPC-157 provided strong gastroprotection against four distinct injury types (stress, ethanol, NSAID, capsaicin neurotoxicity), suggesting a broad protective mechanism involving sensory nerve pathways.
Sikirić, P; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Gjurasin, M; Konjevoda, P; Separović, J; Ljubanović, D; Artuković, B; Bratulić, M; Tisljar, M; Jurina, L; Buljat, G; Miklić, P; Marović, A · Animal Study
RPEP-00384 · 1996BPC-157 demonstrated both prophylactic and therapeutic effects in bile duct ligation-induced pancreatitis, also improving concomitant gastric and duodenal lesions.
Sikirić, P; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Jurina, L; Konjevoda, P; Hanzevacki, M; Ljubanović, D; Separović, J; Gjurasin, M; Bratulić, M; Artuković, B; Jelovac, N; Buljat, G · Animal Study
RPEP-00413 · 1997BPC-157 at 10 µg/kg provided dose-dependent protection against capsaicin-induced rhinitis, reducing mast cell infiltration, degranulation, and inflammatory cell accumulation.
Kalogjera, L; Ries, M; Baudoin, T; Ferencic, Z; Trotic, R; Pegan, B · Animal Study
RPEP-00428 · 1997BPC-157 both protected against NSAID-induced GI lesions and improved chronic adjuvant arthritis, demonstrating simultaneous gastroprotective and anti-inflammatory effects.
Sikiric, P; Seiwerth, S; Grabarevic, Z; Rucman, R; Petek, M; Jagic, V; Turkovic, B; Rotkvic, I; Mise, S; Zoricic, I; Konjevoda, P; Perovic, D; Simicevic, V; Separovic, J; Hanzevacki, M; Ljubanovic, D; Artukovic, B; Bratulic, M; Tisljar, M; Rekic, B; Gjurasin, M; Miklic, P; Buljat, G · Animal Study
RPEP-00561 · 1999BPC-157 demonstrates tissue-protective and regenerative effects across gastrointestinal, musculoskeletal, neurological, and cardiovascular systems, consistently accelerating healing through angiogenesis, anti-inflammation, and NO modulation.
Sikiric, P · Review
RPEP-00586 · 2000Alpha-MSH and its C-terminal tripeptide fragment KPV demonstrated direct antimicrobial activity against S. aureus, C. albicans, and E. coli, establishing a dual anti-inflammatory/antimicrobial function for this neuropeptide.
Catania, A; Cutuli, M; Garofalo, L; Carlin, A; Airaghi, L; Barcellini, W; Lipton, J M · In Vitro
RPEP-00588 · 2000Alpha-MSH and KPV demonstrated broad-spectrum antimicrobial activity including against MRSA and drug-resistant organisms, with an anti-Candida mechanism resembling amphotericin B membrane disruption.
Cutuli, M; Cristiani, S; Lipton, J M; Catania, A · In Vitro
RPEP-00594 · 2000Alpha-MSH modulates inflammation through melanocortin receptor-mediated inhibition of NF-κB signaling, reducing pro-inflammatory cytokines, fever, and immune activation in both peripheral tissues and the central nervous system.
Ichiyama, T; Sato, S; Okada, K; Catania, A; Lipton, J M · Review
RPEP-00619 · 2000Thymosin alpha-1 plasma levels and circadian rhythms were altered in gynecologic inflammation, varying by inflammation type and normalizing with successful treatment.
Shurlygina, A; Litvinenko, G; Dergacheva, T; Trufakin, V · Cohort
RPEP-00628 · 2000Valsartan (angiotensin II type 1 receptor blocker) reduced TNF-α, IL-6, soluble ICAM-1, and BNP in heart failure patients, demonstrating anti-inflammatory effects of angiotensin blockade beyond hemodynamic improvements.
Tsutamoto, T; Wada, A; Maeda, K; Mabuchi, N; Hayashi, M; Tsutsui, T; Ohnishi, M; Sawaki, M; Fujii, M; Matsumoto, T; Kinoshita, M · RCT
RPEP-00653 · 2001Immune cells at sites of inflammation contain and release met-enkephalin, dynorphin A, and beta-endorphin, which activate peripheral opioid receptors on sensory nerves to provide local inflammatory pain control.
Cabot, Peter J; Carter, Laurenda; Schäfer, Michael; Stein, Christoph · Animal Study
RPEP-00672 · 2001Adrenomedullin contributes to both phases of sepsis: beneficial vasodilation during early compensation and harmful cardiovascular collapse during late decompensation, driven by progressive ADM accumulation from reduced clearance and increased tissue production.
Koo, D J; Zhou, M; Chaudry, I H; Wang, P · Review
RPEP-00702 · 2001Plasma BNP correlated with soluble Fas (apoptosis marker) in CHF patients, and sFas independently predicted prognosis, establishing a link between natriuretic peptide signaling and cardiac programmed cell death.
Tsutamoto, T; Wada, A; Maeda, K; Mabuchi, N; Hayashi, M; Tsutsui, T; Ohnishi, M; Fujii, M; Matsumoto, T; Yamamoto, T; Takayama, T; Kinoshita, M · Cross Sectional
RPEP-00707 · 2001Small intestinal ADM mRNA and protein were significantly upregulated during polymicrobial sepsis, with the gut releasing ADM into portal circulation, establishing the intestine as a major source of circulating ADM during sepsis.
Zhou, M; Chaudry, I H; Wang, P · Animal Study
RPEP-00723 · 2002Expanded CRF peptide family including urocortins reveals distinct CRF1 (anxiety/depression) and CRF2 (stress coping/appetite/cardiovascular) receptor functions, enabling receptor-specific drug development.
Dautzenberg, Frank M; Hauger, Richard L · Review
RPEP-00726 · 2002Adrenomedullin acts as both a pro-inflammatory stress responder and an anti-inflammatory tissue protector during disease, with its dual nature and temporal dynamics determining whether it helps or harms at each stage.
Elsasser, Ted H; Kahl, Stas · Review
RPEP-00748 · 2002Pathological burn stress downregulated liver glucocorticoid receptors through inflammatory cytokine (TNF-α, IL-1, IL-6) action, explaining cortisol resistance and uncontrolled inflammation during severe trauma.
Liu, Du-hu; Su, Yong-ping; Zhang, Wei; Lou, Shu-fen; Ran, Xin-ze; Gao, Jing-sheng; Cheng, Tian-min · Animal Study
RPEP-00749 · 2002Adrenomedullin functions as a vasodilator, growth regulator, neurotransmitter, anti-inflammatory agent, and hormone modulator through CRLR/RAMP receptor complexes, with therapeutic implications across cardiovascular, inflammatory, and neoplastic diseases.
López, José; Martínez, Alfredo · Review
RPEP-00769 · 2002Omapatrilat and lisinopril had equivalent effects on angiotensin II, aldosterone, and inflammatory cytokines in CHF, but omapatrilat additionally reduced natriuretic peptide levels, suggesting superior cardiac functional improvement.
Sheth, Tej; Parker, Tom; Block, Alan; Hall, Christian; Adam, Albert; Pfeffer, Mark A; Stewart, Duncan J; Qian, Chunlin; Rouleau, Jean L · RCT
RPEP-00775 · 2002Chronic arthritic pain produced region-specific alterations in dynorphin B, met-enkephalin, and opioid receptor levels across brain, spinal cord, and pituitary, demonstrating multi-level opioid system adaptation to chronic inflammatory pain.
Spetea, Mariana; Rydelius, Gustav; Nylander, Ingrid; Ahmed, Mahmood; Bileviciute-Ljungar, Indre; Lundeberg, Thomas; Svensson, Stefan; Kreicbergs, Andris · Animal Study
RPEP-00820 · 2003KPV (alpha-MSH 11-13) reduced crystal-induced peritonitis as effectively as full-length alpha-MSH via systemic administration, with melanocortin receptor-independent anti-inflammatory activity at the inflammation site.
Getting, Stephen J; Schiöth, Helgi B; Perretti, Mauro · Animal Study
RPEP-00843 · 2003TNF-alpha inhibited TFF3 transcription through NF-κB activation in intestinal cells, creating a pathogenic feedback loop where inflammation simultaneously damages the gut AND suppresses its natural repair peptide.
Loncar, M B; Al-azzeh, E-d; Sommer, P S M; Marinovic, M; Schmehl, K; Kruschewski, M; Blin, N; Stohwasser, R; Gött, P; Kayademir, T · In Vitro
RPEP-00845 · 2003Alpha-MSH and KPV serve triple immune functions: anti-inflammatory (NF-κB inhibition, cytokine suppression), antimicrobial (direct pathogen killing), and immunomodulatory (melanocortin receptor-mediated immune cell regulation) — a comprehensive immune regulatory system.
Luger, Thomas A; Scholzen, Thomas E; Brzoska, Thomas; Böhm, Markus · Review
RPEP-00846 · 2003Early inflammatory pain inhibition was mediated by CRF-triggered opioid release from immune cells, while late inflammation used chemokine (CXCL1/2)-stimulated opioid release — the intrinsic pain control mechanism evolves with inflammation maturation.
Machelska, Halina; Schopohl, Julia K; Mousa, Shaaban A; Labuz, Dominika; Schäfer, Michael; Stein, Christoph · Animal Study
RPEP-00858 · 2003Topical BPC-157 cream reversed methylprednisolone-induced burn wound healing impairment in mice, restoring wound closure rates during concurrent steroid treatment.
Sikiric, P; Seiwerth, S; Mise, S; Staresinic, M; Bedekovic, V; Zarkovic, N; Borovic, S; Gjurasin, M; Boban-Blagaic, A; Batelja, L; Rucman, R; Anic, T · Animal Study
RPEP-00888 · 2004Adrenomedullin has clinical relevance as both a biomarker (predicting outcomes in sepsis, HF, ACS) and a potential therapeutic (improving hemodynamics, protecting kidneys, reducing inflammation) — a dual biomarker-therapy peptide.
Bunton, David C; Petrie, Mark C; Hillier, Chris; Johnston, Fiona; McMurray, John J V · Review
RPEP-00904 · 2004Ghrelin inhibited leptin-induced and activation-induced IL-1β, IL-6, and TNF-α production in human monocytes and T-cells through functional GHS-R on immune cells, establishing an anti-inflammatory role that opposes leptin's pro-inflammatory effects.
Dixit, Vishwa Deep; Schaffer, Eric M; Pyle, Robert S; Collins, Gary D; Sakthivel, Senthil K; Palaniappan, Ravichandran; Lillard, James W; Taub, Dennis D · Animal Study
RPEP-00907 · 2004KPV inhibited NF-κB inflammatory signaling in human keratinocytes through a cAMP-independent mechanism, distinct from full-length alpha-MSH's classical cAMP-dependent MC1R signaling.
Elliott, Richard J; Szabo, Marika; Wagner, Mark J; Kemp, E Helen; MacNeil, Sheila; Haycock, John W · In Vitro
RPEP-00940 · 2004Ghrelin inhibited TNF-α-induced VCAM-1, ICAM-1, and MCP-1 expression in human endothelial cells by blocking NF-κB nuclear translocation via IκBα preservation — a specific anti-inflammatory mechanism protecting blood vessels from atherosclerosis.
Li, Wei Gen; Gavrila, Dan; Liu, Xuebo; Wang, Lixing; Gunnlaugsson, Skuli; Stoll, Lynn L; McCormick, Michael L; Sigmund, Curt D; Tang, Chaosu; Weintraub, Neal L · In Vitro
RPEP-00944 · 2004BPC-157 reversed doxorubicin-induced CHF signs and normalized elevated Big Endothelin-1 levels in rats, comparable to amlodipine and losartan — demonstrating cardioprotective peptide activity against chemotherapy-induced cardiomyopathy.
Lovric-Bencic, Martina; Sikiric, Predrag; Hanzevacki, Jadranka S; Seiwerth, Sven; Rogic, Dunja; Kusec, Vesna; Aralica, Gorana; Konjevoda, Pasko; Batelja, Lovorka; Blagaic, Alenka B · Animal Study
RPEP-00972 · 2004Lactoferrin-derived peptides showed anti-complement activity, inhibiting complement cascade activation and adding immune modulation beyond antimicrobial effects to the lactoferricin functional profile.
Samuelsen, Ørjan; Haukland, Hanne H; Ulvatne, Hilde; Vorland, Lars H · In Vitro
RPEP-01019 · 2005Morphine modified proopiomelanocortin and prodynorphin system activity in immune cells during zymosan-induced peritonitis, demonstrating that exogenous opioid drugs alter the endogenous opioid-immune pain control system at inflammation sites.
Chadzinska, M; Starowicz, K; Scislowska-Czarnecka, A; Bilecki, W; Pierzchala-Koziec, K; Przewlocki, R; Przewlocka, B; Plytycz, B · Animal Study
RPEP-01029 · 2005Ghrelin demonstrates comprehensive immunomodulatory activity: anti-inflammatory cytokine suppression, thymic output enhancement, immune cell function promotion, and potential reversal of age-related immune decline (immunosenescence).
Dixit, Vishwa Deep; Taub, Dennis D · Review