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Mortality in this disease is usually registered within 48\u201372\u00a0h post-hospitalization, the critical period of the illness. It has been recently described that the use of an immunomodulator, whose major component is monomeric ubiquitin (mUb) without the last two glycine residues (Ub\u2206GG), in pediatric human patients with sepsis augments survival. It is known that CXCR4 is the cell receptor of extracellular ubiquitin in humans. This work aimed to explore the effect of one immunomodulator (human Dialyzable Leukocyte Extract-hDLE) as a therapeutic auxiliary in puppies with sepsis and SIRS induced by CPE. We studied two groups of puppies with CPV-2 infection confirmed by polymerase chain reaction. The first group received conventional treatment (CT) and vehicle (V), while the second group received CT plus the immunomodulator (I). We assessed both groups' survival, clinical condition, number of erythrocytes, neutrophils, and lymphocytes during the hospitalization period. In addition, hematocrit, hemoglobin, plasma proteins and cortisol values, as well as norepinephrine\/epinephrine and serotonin concentration were determined. Puppies treated with CT\u2009+\u2009I showed 81% survival, mild clinical signs, and a significant decrease in circulating neutrophils and lymphocytes in the critical period of the treatment. In contrast, the CT\u2009+\u2009V group presented a survival of 42%, severe clinical status, and no improvement of the parameters evaluated in the critical period of the disease. We determined in silico that human Ub\u2206GG can bind to dog CXCR4.\u00a0In conclusion, the\u00a0administration of a human immunomodulator (0.5\u00a0mg\/day\u2009\u00d7\u20095\u00a0days) to puppies with CPE under six months of age reduces the severity of clinical signs, increases survival, and modulates inflammatory cell parameters. Further studies are necessary to take full advantage of these clinical findings, which might be mediated by the human Ub\u2206GG to canine CXCR4 interaction.<\/jats:p>","DOI":"10.1038\/s41598-021-99357-y","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:09:47Z","timestamp":1633651787000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Increased survival in puppies affected by Canine Parvovirus type II using an immunomodulator as a therapeutic aid"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6535-8543","authenticated-orcid":false,"given":"Adriana I.","family":"Mu\u00f1oz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9532-3472","authenticated-orcid":false,"given":"Luis","family":"Vallejo-Castillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5985-675X","authenticated-orcid":false,"given":"Ana","family":"Fragozo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2625-1230","authenticated-orcid":false,"given":"Said","family":"V\u00e1zquez-Leyva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6067-6868","authenticated-orcid":false,"given":"Lenin","family":"Pav\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3878-0631","authenticated-orcid":false,"given":"Gilberto","family":"P\u00e9rez-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1884-8950","authenticated-orcid":false,"given":"Rodolfo","family":"Soria-Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8299-5958","authenticated-orcid":false,"given":"Gabriela","family":"Mellado-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8660-411X","authenticated-orcid":false,"given":"Laura","family":"Cobos-Marin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2818-8522","authenticated-orcid":false,"given":"Sonia Mayra","family":"P\u00e9rez-Tapia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"issue":"1","key":"99357_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.vetmic.2011.09.007","volume":"155","author":"N Decaro","year":"2012","unstructured":"Decaro, N. & Buonavoglia, C. 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