Splenin

A splenic polypeptide identified in the 1980s as a near-twin of thymopoietin, differing at a single active-site residue; its bovine sequence runs 49 residues, while the human 48-residue sequence paper was later retracted.

Also referenced as: Thymopoietin III, Thymopoietin-III, TP-III

Also appears in: Hormone

What is Splenin?

Splenin is a polypeptide isolated from bovine spleen at the start of the 1980s and characterized as a near-identical sibling of thymopoietin, the thymic polypeptide of the same research program. In the bovine sequencing work it runs 49 residues and was given the parallel name thymopoietin III, described there as a monomeric peptide showing minor microheterogeneity at residue 34 (Audhya, Schlesinger, and Goldstein, Biochemistry, 1981;20(21):6195–6200). The durable activity paper places its difference from bovine thymopoietin at that one position — inside the pentapeptide active-site region — and treats it as the change that redirects the molecule’s biological activity (Proceedings of the National Academy of Sciences USA, 1984;81(9):2847–2849). PubChem indexes it as a single defined compound with a listed mass of roughly 4.8 kDa (CID 16132258; CAS 1416-60-0).

It reaches the research-peptide market as a historical artifact rather than on the strength of any active program. Nothing has been added to its file in three decades, its most-quoted descriptive paper was retracted in 1994, and the great majority of products sold under the word “spleen” are organ extracts that have no relationship to this molecule at all.

How it works

The mechanistic case for splenin rests on a small set of papers, most of them from the Goldstein laboratory between 1981 and 1987. The two pentapeptide findings below come from other groups, and describe the synthetic fragment rather than the parent molecule. It is worth reading the bullets as what those groups reported, not as an independently replicated picture.

• A single residue is said to redirect the activity. Splenin was found by a thymopoietin radioimmunoassay that cross-reacted with something in spleen and lymph node but no other tissue. In the bovine molecules it differs from thymopoietin at position 34 alone — aspartic acid in thymopoietin, glutamic acid in splenin. Thymopoietin and its pentapeptide affected neuromuscular transmission and induced T-precursor differentiation while inhibiting B-cell differentiation; splenin and its pentapeptide did not affect neuromuscular transmission, and induced both T- and B-cell precursors (Audhya, Scheid, and Goldstein, Proceedings of the National Academy of Sciences USA, 1984;81(9):2847–2849).
• Activity was localized to residues 32–36. The synthetic pentapeptide splenopentin (Arg-Lys-Glu-Val-Tyr) was reported to reproduce splenin’s activities, as thymopentin (Arg-Lys-Asp-Val-Tyr) does for thymopoietin — the two differing only by that one carboxylate side chain (Singh et al., Immunologic Research, 1998;17(3):345–368).
• A marrow effect was attributed to the fragment, not the parent. Splenopentin (reported as DA SP-5) acted as a co-stimulant for recombinant human GM-CSF in colony formation from human bone-marrow progenitor cells, and preincubation offset the reduction in colony formation caused by AZT. Thymopentin, differing by one residue, did not influence colony formation in the same assay (Diezel et al., International Journal of Immunopharmacology, 1993;15(3):269–273).

Two structural gaps sit underneath all of this. No splenin receptor has ever been identified or cloned, so the “changed receptor specificity” language in the original papers is an inference from differential bioassay rather than a binding result. And splenin has no gene: NCBI Gene returns no record for it, while the gene named for its sibling, TMPO, was found to encode alpha, beta, and gamma proteins that are nuclear — diffuse through the nucleus or localized to the nuclear membrane — expressed in many or all tissues, with the beta form corresponding to the rat lamina-associated polypeptide LAP2, a regulator of nuclear architecture (Harris et al., Genomics, 1995;28(2):198–205). That finding leaves the secreted-thymic-hormone framing that splenin inherited without a clear molecular home, and no equivalent gene-level identity has ever been established for splenin itself.

Research status

The foundational sequence paper is retracted. The report that established the human sequences — and the source of the 48-residue figure that circulates in product copy — was Isolation and complete amino acid sequence of human thymopoietin and splenin (Audhya, Schlesinger, and Goldstein, Proceedings of the National Academy of Sciences USA, 1987;84(11):3545–3549). It was retracted by its authors in the same journal seven years later (Proceedings of the National Academy of Sciences USA, 1994;91(13):6249). PubMed carries the record with a retracted-article flag. The retraction notice is a bare withdrawal and states no reason, so nothing should be read into why beyond the fact of it. The bovine sequencing paper from 1981 and the 1984 activity paper carry no retraction and remain the durable citations.

The retraction did not stand alone. PubMed flags fourteen further papers in the adjacent thymopoietin acetylcholine- and nicotinic-receptor literature as retracted, all withdrawn across 1993 and 1994, including work in Journal of Pharmacology and Experimental Therapeutics (1990;254(3):1113–1119, retracted 1994), Neuroscience (1992;48(3):641–653, retracted 1994), and Brain Research (1992;599(1):117–128, retracted 1993). Those papers concern thymopoietin rather than splenin, but they matter here because splenin’s defining contrast — that it does not act at the neuromuscular junction where thymopoietin does — is drawn against exactly that body of work.

No human trials of splenin exist. ClinicalTrials.gov returns zero registered studies for splenin and zero for splenopentin. No trial of the intact polypeptide has been published in any phase.

The only human data in this family comes from a modified fragment. Diacetyl-splenopentin (BCH 069, later Berlopentin) — an acetylated pentapeptide, not splenin — was taken into early-phase testing in East Germany around 1990. A Phase I study concluded it was well tolerated, with a flush and sensation of heat during intravenous administration at the more concentrated 50 mg/10 mL preparation but not at 50 mg/20 mL, and with changes in triglycerides, transaminases, lipase, and hemoglobin that stayed inside normal laboratory ranges (Simon et al., Allergie und Immunologie (Leipzig), 1990;36(4):245–251). A companion hay-fever study produced a clearly split result: intravenous BCH 069 was significantly better than placebo at reducing clinical symptoms, while subcutaneous administration was not effective. The arms were not matched on schedule — both gave 50 mg three times weekly, but the intravenous course ran six weeks against four for the subcutaneous — so route and duration are confounded in that comparison (Simon et al., Allergologia et Immunopathologia (Madrid), 1990;18(3):155–160). Two further Phase I analyses found no significant effect on caffeine clearance (Simon et al., Die Pharmazie, 1992;47(1):49–50) and no significant change in prolactin, LH, TSH, cortisol, testosterone, progesterone, or estradiol (Simon et al., Experimental and Clinical Endocrinology, 1990;96(3):314–316). The program did not continue, and no product reached approval.

The literature is dormant. A PubMed search for “splenin” returns roughly 134 records, and the substantive biochemical work is essentially all pre-1995. Most post-1995 hits use the word in the unrelated extract sense described below.

Common dosage forms

Splenin is not an FDA-approved drug and has no approved or compounded product anywhere. A DailyMed search for splenin returns no labels, and openFDA returns no drug-label match. Where the defined polypeptide appears in the research market at all, it is as a lyophilized powder in a sealed vial at small milligram fills for reconstitution, the standard research format.

Far more of what is shelved under “spleen peptide” is an extract rather than this molecule. DailyMed lists dozens of bovine and porcine (suis) spleen preparations sold as liquids, sprays, and homeopathic combination products. A separate family of spleen extracts — spleen aminopeptide oral solution and oral lyophilized powder — is manufactured and studied in China as an immunomodulator, with its own trial literature (for example, Anti-Cancer Drugs, 2021;32(10):1067–1075). Organ-peptide capsule lines in the Khavinson bioregulator tradition likewise sell tissue-derived preparations under organ names. None of these is a defined 49-residue polypeptide, and a capsule or oral solution is a strong signal that a product is an extract. This section describes formats only and is not dosing guidance.

Key considerations

• The headline numbers trace to a withdrawn paper. The commonly repeated “48-amino-acid” description of splenin comes from the 1987 human sequencing report, which its own authors retracted in 1994. So does the occasional claim that bovine splenin and thymopoietin differ at two positions, 34 and 43 — that sentence appears in the retracted paper, while the durable 1984 activity paper states the two differ only in position 34. The bovine length of 49 residues, from the 1981 Biochemistry paper, has never been withdrawn. Vendor and aggregator copy generally quotes the retracted figure without noting its status, and some sources hedge to “48–49 amino acids” without explaining why the range exists.
• “Splenin” names two unrelated things, and the clinical literature uses the other one. In Soviet and post-Soviet medicine, splenin (Спленин, latinized Spleninum) is a bovine spleen extract preparation used as an immunocorrector. It appears in Russian- and Ukrainian-language clinical papers alongside thymalin, thymogen, and erbisol — for instance in perioperative regimens for elderly cancer patients (Voprosy Onkologii, 1991;37(7–8):873–877), in immune-correction work in diabetic retinopathy (Likars’ka Sprava, 2001;(1):53–56), and in herbicide-induced immunodeficiency models (Gigiena i Sanitariia, 2003;(3):55–57). A literature search on the bare word returns these extract studies mixed in with the polypeptide work, and they are not evidence for the defined molecule.
• Splenopentin is a different compound. The pentapeptide fragment corresponding to residues 32–36, and its acetylated derivative BCH 069, are separate molecules with their own — still very thin — record. Evidence generated for the pentapeptide does not transfer to the intact polypeptide, and the only human dosing experience in this family belongs to the fragment.
• No modern molecular identity. There is no splenin gene, no identified receptor, and no recombinant standard. The related TMPO gene turned out to encode nuclear architectural proteins rather than a secreted hormone, which leaves the original endocrine framing unresolved rather than confirmed. Identity and purity for any material sold under this name therefore rest entirely on a certificate of analysis reporting sequence and observed mass.
• There is no human safety data for splenin itself. What safety information exists in this family belongs to the acetylated pentapeptide, where an intravenous flush reaction was concentration-dependent and the subcutaneous arm — on a shorter course — produced no clinical effect. Nothing has been published on the intact polypeptide in humans at any dose or by any route.