PMID- 9698765
OWN - NLM
STAT- MEDLINE
DCOM- 19981020
LR  - 20190516
IS  - 0100-879X (Print)
IS  - 0100-879X (Linking)
VI  - 31
IP  - 5
DP  - 1998 May
TI  - Cytokines produced by susceptible and resistant mice in the course of 
      Paracoccidioides brasiliensis infection.
PG  - 615-23
AB  - Paracoccidioidomycosis (PCM) is the most prevalent deep mycosis in Latin America 
      and presents a wide spectrum of clinical manifestations. We established a 
      genetically controlled murine model of PCM, where A/Sn mice develop an infection 
      which mimics the benign disease (immune responses which favor cellular immunity) 
      and B10.A animals present the progressive disseminated form of PCM (preferential 
      activation of B cells and impairment of cellular immune responses). To understand 
      the immunoregulatory phenomena associated with resistance and susceptibility in 
      experimental PCM, A/Sn and B10.A mice were studied regarding antigen-elicited 
      secretion of monokines (TNF-alpha and TGF-beta) and type-1 (IL-2 and IFN-gamma) 
      and type-2 (IL-4,5,10) cytokines. Total lymph node cells from resistant mice 
      infected i.p. with P. brasiliensis produced early and sustained levels of 
      IFN-gamma and IL-2; type-2 cytokines (IL-4 and IL-5) started to appear 8 weeks 
      after infection. In contrast, susceptible mice produced low levels of IFN-gamma 
      concomitant with significant levels of IL-5 and IL-10 early in the infection. In 
      the chronic phase of the disease, susceptible animals presented a transitory 
      secretion of IL-2, and IL-4. In the pulmonary infection IL-4, IL-5 and IL-10 were 
      preferentially detected in the lung cells washings of susceptible animals. After 
      in vitro challenge with fungal antigens, normal peritoneal macrophages from B10.A 
      mice secreted high levels of TGF-beta and low levels of TNF-alpha. In contrast, 
      macrophages from A/Sn animals released high levels of TNF-alpha associated with a 
      small production of TGF-beta. The in vivo depletion of IFN-gamma not only 
      abrogated the resistance of A/Sn mice but also diminished the relative resistance 
      of B10.A animals. The in vivo depletion of IL-4 did not alter the disease 
      outcome, whereas administration of rIL-12 significantly enhanced resistance in 
      susceptible animals. Taken together, these results suggest that an early 
      secretion of high levels of TNF-alpha and IFN-gamma followed by a sustained 
      secretion of IL-2 and IFN-gamma plays a dominant role in the resistance 
      mechanisms to P. brasiliensis infection. In contrast, an early and ephemeral 
      secretion of low levels of TNF-alpha and IFN-gamma associated with production of 
      IL-5, IL-10 and TGF-beta characterizes the progressive disease of susceptible 
      animals.
FAU - Calich, V L
AU  - Calich VL
AD  - Departamento de Imunologia, Instituto de Ciencias Biomedicas, Universidade de Sao 
      Paulo, Brasil. vlcalich@biomed.icb2.usp.br
FAU - Kashino, S S
AU  - Kashino SS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Brazil
TA  - Braz J Med Biol Res
JT  - Brazilian journal of medical and biological research = Revista brasileira de 
      pesquisas medicas e biologicas
JID - 8112917
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - Cytokines/*biosynthesis
MH  - Disease Susceptibility
MH  - Immunity, Innate
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Paracoccidioidomycosis/genetics/*immunology/metabolism
RF  - 23
EDAT- 1998/08/12 00:00
MHDA- 1998/08/12 00:01
CRDT- 1998/08/12 00:00
PHST- 1998/08/12 00:00 [pubmed]
PHST- 1998/08/12 00:01 [medline]
PHST- 1998/08/12 00:00 [entrez]
AID - 10.1590/s0100-879x1998000500003 [doi]
PST - ppublish
SO  - Braz J Med Biol Res. 1998 May;31(5):615-23. doi: 10.1590/s0100-879x1998000500003.