Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in combined injured mice. (2nd September 2015)

• Record Type: Journal Article
• Authors: Elliott, Thomas B.; Bolduc, David L.; Ledney, G. David; Kiang, Juliann G.; Fatanmi, Oluseyi O.; Wise, Stephen Y.; Romaine, Patricia L. P.; Newman, Victoria L.; Singh, Vijay K.
• Is Part Of: International journal of radiation biology. Volume 91:Number 9(2015:Sep.)
• Page Start: 690
• Page End: 702
• Publication Date: 2015-09-02
• Subjects: Anti-microbial therapy -- bacterial translocation -- cytokines -- chemokines -- gamma-radiation -- immunomodulator -- infection -- mice -- sepsis; Radiation -- Physiological effect -- Periodicals; Radiobiology -- Periodicals; 571.45
• DOI: 10.3109/09553002.2015.1054526
• Languages: English
• ISSNs: 0955-3002

Abstract

Abstract : Purpose : A combination therapy for combined injury (CI) using a non-specific immunomodulator, synthetic trehalose dicorynomycolate and monophosphoryl lipid A (STDCM-MPL), was evaluated to augment oral antimicrobial agents, levofloxacin (LVX) and amoxicillin (AMX), to eliminate endogenous sepsis and modulate cytokine production. Materials and methods : Female B6D2F1 /J mice received 9.75 Gy cobalt-60 gamma-radiation and wound. Bacteria were isolated and identified in three tissues. Incidence of bacteria and cytokines were compared between treatment groups. Results : Results demonstrated that the lethal dose for 50% at 30 days (LD50/30 ) of B6D2F1 /J mice was 9.42 Gy. Antimicrobial therapy increased survival in radiation-injured (RI) mice. Combination therapy increased survival after RI and extended survival time but did not increase survival after CI. Sepsis began five days earlier in CI mice than RI mice with Gram-negative species predominating early and Gram-positive species increasing later. LVX plus AMX eliminated sepsis in CI and RI mice. STDCM-MPL eliminated Gram-positive bacteria in CI and most RI mice but not Gram-negative. Treatments significantly modulated 12 cytokines tested, which pertain to wound healing or elimination of infection. Conclusions : Combination therapy eliminates infection and prolongs survival time but does not assure CI mouse survival, suggesting that additional treatment for proliferative-cell recovery is required.