title: Protective effects of ulinastatin on proliferation and cytokine release of splenocytes from rats with severe acute pancreatitis.
abstract: OBJECTIVE
  To clarify the contributions of ulinastatin to cellular immune responses in vivo, we examined the functional alterations of splenocytes and quantitatively evaluated the effects of ulinastatin on the splenocyte function during experimental severe acute pancreatitis.
  
  
  METHODS
  Severe acute pancreatitis was induced in rats by retrograde injection of 3% sodium deoxycholate. Thirty minutes after induction of pancreatitis, the rats were randomly assigned to four groups, receiving either saline or 50,000 U/kg of ulinastatin, respectively. Splenocytes were obtained aseptically and stimulated with concanavalin A for 24 h. Then the proliferative activity of cultured splenocytes was measured by using an MTT cellular proliferation assay, and the cytokine concentrations in the culture supernatants were measured by enzyme-linked immunosorbent assays.
  
  
  RESULTS
  Upon stimulation, the release of interleukin-2, interleukin-10, and interferon-gamma was significantly decreased in the splenocytes from rats with pancreatitis as compared with those from sham operation and control groups. The splenocyte proliferation was also significantly suppressed in this group. In contrast, the proliferative as well as the cytokine-releasing capacities of the splenocytes from rats treated with ulinastatin were significantly increased as compared with those from rats with pancreatitis.
  
  
  CONCLUSIONS
  The deficiencies in proliferation and cytokine release in response to antigen stimulation demonstrated an anergic state of splenocytes during severe acute pancreatitis. Treatment with ulinastatin contributed to the recovery of the immune function by improving proliferative responses and cytokine release of splenocytes. These data suggest that a protease-modulating therapy may be an effective strategy for the treatment of immunosuppression induced by severe acute pancreatitis.
authors.affiliation: Department of Surgery, General Hospital of the Tianjin Medical University, Tianjin, China. mataoemail@yahoo.com.cn
authors.forename: Tao
authors.initials: T
authors.lastname: Ma
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Shao
authors.forename: Qinghui
authors.initials: Q
authors.lastname: Qi
authors.forename: Wenquan
authors.initials: W
authors.lastname: Hu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D010195:Pancreatitis / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects*; D014361:Trypsin Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D006023:Glycoproteins; D007376:Interleukin-2; D014361:Trypsin Inhibitors; D016753:Interleukin-10; D007371:Interferon-gamma; C028665:urinastatin