Alleviation of Renal and Pulmonary Injury by Immunomodulation in leptospirosis: Hamster Model(cid:31)
Kearkiat Praditpornsilpa MD*, Noppadon Sangjun DVM**, Wipawee Kittikowit MD***, Duangporn Phulsuksombati DVM***, Yingyos Avihingsanon MD*, Talerngsak Kansanabuch MD*, Kriang Tungsanga MD*, Somchai Eiam-Ong MD*
Affiliation : (cid:31) Research granted by Ratchadapiseksompotch Fund * Division of Nephrology,Department of Medicine,Faculty of Medicine,Chulalongkorn University Hospital ** Thai Component-Armed Forces Research Institute of Medical Sciences *** Department of Pathology, Faculty of Medicine, Chulalongkorn University Hospital
Objective : Severe leptospirosis manifestations include acute renal failure, caused by acute interstitial nephri-
tis and pulmonary hemorrohage. Spirochete invasion and toxicity of outer membrane cause robust inflamma-
tory host responses. These responses lead to the generation of cytokines, chemokines, and inflammatory cell
infiltrations which result in severe organ dysfunctions. The immunomodulation by the modulation of host
immune response may alleviate the renal and pulmonary injury. The authors determined whether the current
immunosuppressive agents could alleviate the inflammation and minimize the organ injury in hamster model.
Materials and Methods : The animal experiments were conducted with the approval of The Ethical Research
Committee of Chulalongkorn University Hospital. The leptospira interrogan serovar pyrogenese was isolated
from a wild rat. The spirochete was grown in Fletcher’s semisolid media and after subcultures were transferred
to the Fletcher’s liquid media. An amount of 0.5 ml of the spirochete culture media containing 1 x 108 lepto-
spires/ml was intraperitoneally injected to golden Syrian hamsters (Mesocrietus auratus), age 4-6 weeks,
weighing 60-80 grams. The hamsters were randomed into 5 groups (n = 4 in each group) namely, 1) Normal
group (Control group), 2) Leptospira group, 3) CsA group (leptospira with cyclosporine feeding, 100 mg/kg/
day), 4) Rapa group (leptospira with rapamicin feeding, 0.6 mg/kg/day), and 5) Irra group (leptospira with
irradiation). Cyclosporine and rapamicin were started at day 0 after the spirochete injection. Gamma ray
dose 200 cGy was irradiated to the hamster 3 days before the spirochete inoculation. The animals were
autopsied or euthanized if expired or at day 5 post inoculation. The blood samples for BUN, and creatinine
were drawn before the inoculation and at autopsy or euthanasia.
Results : The inoculation of L Interrogan 0.5 ml (1 x 108 leptospires/ml) without immunomodulation cause
mortality of all animals at day 4 or day 5 post inoculation. The blood chemistry showed acute severe azotemia.
The autopsy findings revealed severe interstitial nephritis and severe pulmonary hemorrhage. The hamsters in
the Rapa group had only minimal pulmonary hemorrhage and minimal focal interstitial inflammation of
kidney. There were cytoadherance of inflammatory cells to the endothelial cells in lungs and kidneys without
the intrusion into the interstitium. The blood chemistry in Rapa group showed mild elevation of BUN and Cr.
The immunomodulation by cyclosporine and irradiation did not alleviate the disease. On the contrary,
cyclosporine and irradiation caused more severe histopathology.
Conclusion : The immunomodulation by rapamicin in leptospirosis in hamsters could alleviate the kidney and
pulmonary injuries. The up-regulation of IL-2 in peripheral blood lymphocytes did not result in the kidney and
pulmonary injuries.
Keywords : Hamster leptospirosis, Cyclosporine, Rapamicin, Irradiation
