Kinetics of inflammatory cytokines in patients with scrub typhus receiving doxycycline treatment.
OBJECTIVE
Animal models have suggested that various cytokines and chemokines play an important role in host defense against Orientia tsutsugamushi, however, human data are limited. We investigated the kinetics of inflammatory responses in patients with scrub typhus receiving doxycycline.


METHODS
Amongst patients being treated for scrub typhus, serially collected sera were tested for TNF-alpha, IFN-gamma, IL-2, IL-4, IL-5, and IL-10 by immunoassay. The mRNAs encoding TNF-alpha, IL-1 beta, IL-6, IL-8, IFN-gamma, IL-12, IL-2, IL-4, IL-5, and IL-10 were measured by semiquantitative reverse transcription-PCR.


RESULTS
The concentrations of TNF-alpha, IFN-gamma, and IL-10 of patients prior to doxycycline treatment were significantly higher than those of healthy volunteers. They decreased markedly within 24h after starting doxycycline. The mRNAs for IL-1 beta, TNF-alpha, IL-6, IFN-gamma, and IL-10 were highly expressed. Expression of mRNAs for IL-1 beta, IFN-gamma, and IL-10 decreased at day 2-7 of doxycycline treatment.


CONCLUSIONS
Inflammatory cytokines including TNF-alpha, IL-1 beta, and IL-6 are markedly upregulated in patients with scrub typhus. Doxycycline treatment rapidly reduces the production of these cytokines, corresponding to the early defervescence after the start of the treatment. The profiles of T cell-derived cytokines in patients with scrub typhus do not follow typical Th1 or Th2 patterns.
Chung
Doo Ryeon
DR
Division of Infectious Diseases, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 896 Pyeongchon-dong, Dongan-gu, Anyang-si, Gyeonggi-do 431-070, South Korea. dr.chung@samsung.com
Lee
Young Seok
YS
Lee
Seung Soon
SS
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004318:Doxycycline / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012612:Scrub Typhus / Q000188:drug therapy* / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics
D000900:Anti-Bacterial Agents; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004318:Doxycycline