PMID- 10886398
OWN - NLM
STAT- MEDLINE
DCOM- 20000718
LR  - 20230412
IS  - 0019-2805 (Print)
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 100
IP  - 2
DP  - 2000 Jun
TI  - Levamisole induces interleukin-18 and shifts type 1/type 2 cytokine balance.
PG  - 217-24
AB  - Immune responses can be classified, according to the predominant cytokines 
      involved, into type 1 (featuring interferon-gamma, IFN-gamma) and type 2 
      (featuring interleukin-4, IL-4); imbalance between type 1 and type 2 cytokine 
      compartments has been implicated in many human diseases. Levamisole is a drug 
      with an unknown mode of action that has been used to boost immunity in infectious 
      diseases including leprosy, and in some cancers. To test the hypothesis that 
      levamisole acts by inducing a shift to a type 1 immune response, we used Brown 
      Norway (BN) rats, which are markedly biased to type 2 responses. BN rats treated 
      with levamisole showed a dose-dependent rise in serum IFN-gamma and fall in serum 
      immunoglobulin E (IgE) level. Detailed analysis of cytokine gene expression 
      showed upregulation of IFN-gamma and downregulation of IL-4 messenger RNA. This 
      coincided with marked upregulation of IL-18, a recently characterized cytokine 
      with potent activity in stimulating IFN-gamma production. IL-12 was not induced. 
      Further, the type 2 response induced in BN rats by mercuric chloride was markedly 
      attenuated when rats were pretreated with levamisole: there was a 2-log reduction 
      in maximum serum IgE level and marked attenuation of IL-4 gene upregulation. 
      These data indicate that levamisole acts by resetting the immune balance towards 
      a type 1 response via induction of IL-18. Our findings provide a direction for 
      development of more specific immunomodulating therapy.
FAU - Szeto, C
AU  - Szeto C
AD  - Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, UK.
FAU - Gillespie, K M
AU  - Gillespie KM
FAU - Mathieson, P W
AU  - Mathieson PW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antinematodal Agents)
RN  - 0 (Interleukin-18)
RN  - 207137-56-2 (Interleukin-4)
RN  - 2880D3468G (Levamisole)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 53GH7MZT1R (Mercuric Chloride)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adjuvants, Immunologic/*pharmacology
MH  - Animals
MH  - Antinematodal Agents/*pharmacology
MH  - Dose-Response Relationship, Immunologic
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Immunoglobulin E/blood
MH  - Interferon-gamma/blood/genetics
MH  - Interleukin-18/genetics/*metabolism
MH  - Interleukin-4/genetics/metabolism
MH  - Levamisole/*pharmacology
MH  - Male
MH  - Mercuric Chloride/antagonists & inhibitors
MH  - Rats
MH  - Rats, Inbred BN
MH  - Th2 Cells/drug effects/immunology
PMC - PMC2327010
EDAT- 2000/07/11 11:00
MHDA- 2000/07/25 11:00
PMCR- 2001/06/01
CRDT- 2000/07/11 11:00
PHST- 2000/07/11 11:00 [pubmed]
PHST- 2000/07/25 11:00 [medline]
PHST- 2000/07/11 11:00 [entrez]
PHST- 2001/06/01 00:00 [pmc-release]
AID - imm042 [pii]
AID - 10.1046/j.1365-2567.2000.00042.x [doi]
PST - ppublish
SO  - Immunology. 2000 Jun;100(2):217-24. doi: 10.1046/j.1365-2567.2000.00042.x.