title: Streptozotocin-associated lymphopenia in cynomolgus monkeys.
abstract: Streptozotocin (STZ) is used to induce diabetes in experimental animals. It has a variety of adverse effects, ranging from nausea, emesis, and weight loss to liver damage, renal failure, and metabolic acidosis. STZ also has effects on the immune system, being associated with lymphopenia in rodents, the mechanism of which is not fully understood. We present data on a significant STZ-associated reduction in lymphocyte count in nonhuman primates. We report a significant reduction in absolute lymphocyte count; in 2 monkeys, the lymphopenia persisted for >100 d. However, a significant increase in absolute monocyte count was noted. Furthermore, an increase in serum monocyte chemoattractant protein-1 (MCP-1) was observed. The reduction in lymphocyte numbers may contribute to immunomodulation that may be beneficial to a subsequent islet graft, and may reduce the need for immunosuppressive therapy. The increase in monocytes and MCP-1, however, may be detrimental to the islet graft. Studies are warranted to explore the mechanism by which STZ has its effect.
authors.affiliation: Thomas E. Starzl Transplantation Institute; University of Pittsburgh Medical Center ; Pittsburgh , PA USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Nagaraju
authors.affiliation: Division of Immunogenetics; Department of Pediatrics; Children's Hospital of Pittsburgh; University of Pittsburgh Medical Center ; Pittsburgh , PA USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Bertera
authors.affiliation: Division of Immunogenetics; Department of Pediatrics; Children's Hospital of Pittsburgh; University of Pittsburgh Medical Center ; Pittsburgh , PA USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Funair
authors.affiliation: Thomas E. Starzl Transplantation Institute; University of Pittsburgh Medical Center ; Pittsburgh , PA USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Wijkstrom
authors.affiliation: Division of Immunogenetics; Department of Pediatrics; Children's Hospital of Pittsburgh; University of Pittsburgh Medical Center ; Pittsburgh , PA USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Trucco
authors.affiliation: Thomas E. Starzl Transplantation Institute; University of Pittsburgh Medical Center ; Pittsburgh , PA USA.
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
authors.affiliation: Division of Immunogenetics; Department of Pediatrics; Children's Hospital of Pittsburgh; University of Pittsburgh Medical Center ; Pittsburgh , PA USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Bottino
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000097:blood / Q000139:chemically induced*; D008252:Macaca fascicularis; D013311:Streptozocin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D018932:Chemokine CCL2; D006442:Glycated Hemoglobin; D013311:Streptozocin
keywords: STZ, streptozotocin; WBC, white blood cell; cynomolgus; diabetes; islets; lymphopenia; monkey; monocytes; pig; streptozotocin