PMID- 20677939
OWN - NLM
STAT- MEDLINE
DCOM- 20100909
LR  - 20240502
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 202
IP  - 6
DP  - 2010 Sep 15
TI  - Paucity of initial cerebrospinal fluid inflammation in cryptococcal meningitis is 
      associated with subsequent immune reconstitution inflammatory syndrome.
PG  - 962-70
LID - 10.1086/655785 [doi]
AB  - BACKGROUND: Cryptococcal meningitis (CM)-related immune reconstitution 
      inflammatory syndrome (IRIS) complicates antiretroviral therapy (ART) in 20%-40% 
      of ART-naive persons with AIDS and prior CM. Pathogenesis is unknown. METHODS: We 
      compared initial cerebrospinal fluid (CSF) cultures, inflammatory markers, and 
      cytokine profiles in ART-naive patients with AIDS who did or did not subsequently 
      develop IRIS after starting ART. We also compared results obtained at IRIS events 
      or CM relapse. RESULTS: Of 85 subjects with CM, 33 (39%) developed CM-related 
      IRIS and 5 (6%) developed culture-positive CM relapse. At CM diagnosis, subjects 
      subsequently developing IRIS had less inflammation, with decreased CSF 
      leukocytes, protein, interferon-gamma, interleukin-6, interleukin-8, and tumor 
      necrosis factor-alpha, compared with subjects not developing IRIS (P<.05, for 
      each). Initial CSF white blood cell counts < or =25 cells/microL and protein 
      levels < or =50 mg/dL were associated with development of IRIS (odds ratio, 7.2 
      [95% confidence interval, 2.7-18.7]; P<.001). Compared with baseline levels, we 
      identified CSF elevations of interferon-gamma, tumor necrosis factor-alpha, 
      granulocyte colony-stimulating factor, vascular-endothelial growth factor, and 
      eotaxin (CCL11) (P<.05, for each) at the time of IRIS but minimal inflammatory 
      changes in those with CM relapse. CONCLUSIONS: Patients who subsequently develop 
      CM-related IRIS exhibit less initial CSF inflammation at the time of CM 
      diagnosis, compared with those who do not develop IRIS. The inflammatory CSF 
      cytokine profiles observed at time of IRIS can distinguish IRIS from CM relapse.
FAU - Boulware, David R
AU  - Boulware DR
AD  - Division of Infectious Diseases & International Medicine, Department of Medicine, 
      University of Minnesota, Minneapolis, Minnesota, USA. boulw001@umn.edu
FAU - Bonham, Shulamith C
AU  - Bonham SC
FAU - Meya, David B
AU  - Meya DB
FAU - Wiesner, Darin L
AU  - Wiesner DL
FAU - Park, Gregory S
AU  - Park GS
FAU - Kambugu, Andrew
AU  - Kambugu A
FAU - Janoff, Edward N
AU  - Janoff EN
FAU - Bohjanen, Paul R
AU  - Bohjanen PR
LA  - eng
GR  - K23 AI073192-01A2/AI/NIAID NIH HHS/United States
GR  - R03AI078750-01/AI/NIAID NIH HHS/United States
GR  - T32 AI055433-05/AI/NIAID NIH HHS/United States
GR  - R03 AI078750/AI/NIAID NIH HHS/United States
GR  - L30 AI066779-03/AI/NIAID NIH HHS/United States
GR  - K12 RR023247/RR/NCRR NIH HHS/United States
GR  - K23 AI073192/AI/NIAID NIH HHS/United States
GR  - K12RR023247-04/RR/NCRR NIH HHS/United States
GR  - R03 AI078750-02/AI/NIAID NIH HHS/United States
GR  - L30 AI066779/AI/NIAID NIH HHS/United States
GR  - K12 RR023247-04/RR/NCRR NIH HHS/United States
GR  - L30AI066779/AI/NIAID NIH HHS/United States
GR  - T32AI055433-05/AI/NIAID NIH HHS/United States
GR  - K23AI073192-01A2/AI/NIAID NIH HHS/United States
GR  - T32 AI055433/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
SB  - IM
MH  - Acquired Immunodeficiency Syndrome/*complications/drug therapy
MH  - Cerebrospinal Fluid/chemistry/*immunology/*microbiology
MH  - Cryptococcus neoformans/*immunology
MH  - Cytokines/analysis
MH  - Diagnosis, Differential
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/*microbiology/*pathology
MH  - Inflammation Mediators/analysis
MH  - Meningitis, Cryptococcal/*complications/immunology/pathology
MH  - Recurrence
MH  - Severity of Illness Index
PMC - PMC2924457
MID - NIHMS214006
COIS- Conflicts of Interest: No conflicts of interest exist.
EDAT- 2010/08/04 06:00
MHDA- 2010/09/10 06:00
PMCR- 2011/09/15
CRDT- 2010/08/04 06:00
PHST- 2010/08/04 06:00 [entrez]
PHST- 2010/08/04 06:00 [pubmed]
PHST- 2010/09/10 06:00 [medline]
PHST- 2011/09/15 00:00 [pmc-release]
AID - 10.1086/655785 [doi]
PST - ppublish
SO  - J Infect Dis. 2010 Sep 15;202(6):962-70. doi: 10.1086/655785.