In vivo alterations in cytokine production following interleukin-12 (IL-12) and anti-IL-4 antibody treatment of CB6F1 mice with chronic cutaneous leishmaniasis

Li, J; Scott, Phillip; Farrell, Jay P.

doi:10.1128/iai.64.12.5248-5254.1996

Cited by 19 publications

(6 citation statements)

References 21 publications

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“…Direct measurement of parasite growth in both groups of mice on day 56 using serial dilution plating revealed mice treated with HgCl 2 harbored approximately 10 10 parasites per footpad whereas PBS‐treated mice carried less than 1000 parasites per footpad (Figure 1b). These loads (approximately 10 10 ) are similar to those observed in other studies reporting mice with similar lesion sizes (18,19) and may reflect the exquisite susceptibility acquired by these normally resistant animals after HgCl 2 administration.…”

Section: Resultssupporting

confidence: 86%

Mercury enhances susceptibility to murine leishmaniasis

Bagenstose

Mentink‐Kane

Brittingham

et al. 2001

Parasite Immunology

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The genetic background of mice infected with Leishmania major determines the response to infection, resulting in a resistant or susceptible phenotype. Susceptible mice develop a T-helper type 2 (Th2)-type immune response following infection distinguished by the development of interleukin (IL)-4 secreting T cells in the lymph node and spleen. In SJL mice, which normally heal L. major lesions, subtoxic doses of mercury induce an autoimmune syndrome characterized by an expansion of Th2 cells. In this study, we examined the effect of mercury administration on the outcome of L. major infection in SJL mice. We show that subtoxic doses of mercuric chloride (HgCl2) exacerbate disease outcome in SJL mice resulting in increased footpad swelling and increased parasite burdens. Furthermore, the effects of HgCl2 treatment on resistance to L. major are time-dependent. The nonhealing phenotype was observed only if mice had been treated with HgCl2 prior to L. major infection for at least 1 week, a timepoint at which mice treated with HgCl2 alone had increased splenocyte IL-4 production. HgCl2 treatment also increased production of serum immunoglobulin (Ig)E and IgG1, two IL-4 dependent isotypes. These results show that HgCl2 treatment enhances the susceptibility to L. major in SJL mice, consistent with the induction of host Th2 parameters. These findings have implications for the role of mercury contamination in areas of endemic leishmaniasis.

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Section: Resultssupporting

confidence: 86%

Mercury enhances susceptibility to murine leishmaniasis

Bagenstose

Mentink‐Kane

Brittingham

et al. 2001

Parasite Immunology

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“…Our finding confirms those data suggesting that successful treatment in leishmaniasis requires not only a reduction in parasite number, but also the development of an effective cell‐mediated immune response [ 20, 22, 23]. Recently, successful therapy of chronic nonhealing murine cutaneous leishmaniasis has been shown using a combined therapy of IL‐12, IFN‐γ or anti‐IL‐4 plus pentostam (Pentavalent antimony compound) [ 20, 22, 23].…”

Section: Discussionsupporting

confidence: 87%

“…Extensive research is currently focused on attempts to shift the immune response towards a protective cytokine pattern [ 20, 21–24]. We suggest that garlic may induce a Th1‐type cytokine pattern, considering the stimulation of the cell‐mediated responses such as T‐cell proliferation and macrophage activation by garlic [ 12–18].…”

Section: Discussionmentioning

confidence: 99%

Garlic Induces a Shift in Cytokine Pattern in Leishmania major‐Infected BALB/c Mice

et al. 2000

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The regulation of T helper (Th)1‐ and Th2‐type cytokine patterns is important in the final outcome of leishmaniasis in human and murine models. We examined the efficacy of garlic therapy or a combination of garlic and an antimonial drug (glucantime) in promoting healing and regulation of Th1/Th2 cytokine patterns in highly susceptible BALB/c mice infected with Leishmania major. Separate groups of infected mice received 20 mg/kg/day garlic, 60 mg/kg/day glucantime or a combination of the two, from day 30 after infection for 2 weeks. An enzyme‐linked immunosorbant assay ( ELISA) was performed on spleen cell culture supernatants for interferon(IFN)‐γ interleukin(IL)‐2, IL‐4 and IL‐10. The results indicate that garlic therapy is more effective than the usual antileishmanial drug in curing the infection. Garlic‐treated mice developed Th1‐type cytokine responses. In contrast, glucantime therapy led to a Th2‐type response in the control group with a lower level of IL‐2. However, a combination of garlic and glucantime treatment was more effective than either treatment alone, and resulted in a Th1‐type response similar to that which developed with garlic treatment. These results suggest that garlic extract in combination with an antimonial drug, may provide effective therapy against L. major. The immunomodulatory properties of garlic were elucidated in terms of shifting the cytokine response to a Th1‐type pattern and therefore causing the protective response.

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“…One of the strongest examples of the role of IL‐4 in inducing Th2 polarization and the ability of the type 1 immune response in preventing Th2 polarization is the experimental model of leishmaniasis. After infection with Leishmania major , BALB/c mice develop a severe form of leishmaniasis, whereas C57BL/6 mice control Leishmania growth and develop only mild disease (60). Whereas neutralization of IL‐4 in BALB/c promotes a type 1 immune response and control of the infection (61), neutralization of IL‐12 or IFN‐γ in L. major ‐infected C57BL/6 resulted in dissemination of infection (62).…”

Section: Th2 Polarization In Helminth Infection and Asthmamentioning

confidence: 99%

Worms and allergy

Carvalho

Bastos

Araújo

2006

Parasite Immunology

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Worms and asthma are associated with a type 2 immune response, but evidence has accumulated that helminth infection is negatively associated with atopy, prevalence of allergic diseases and severity of asthma. One important difference between these polarized type 2 responses is that in allergy modulation of the immunological response is not appropriate, whereas in infection with helminths, several host mechanisms down-regulate the host immune response. As a result, patients infected with worms have a decrease in both type 1 and type 2 responses. The main mechanism involved in this down-modulation is increased production of IL-10, but expansion of regulatory T cells and NKT cells may also participate. Regarding the interaction between worms and allergy, a few variables need to be taken in account: phase (acute or chronic) of helminth infection, parasite load and species of helminth. In animals and humans, acute helminth infection may increase manifestations of allergy, whereas chronic infection with parasites decreases atopy. The modulation of the immune response by helminths is dependent on having an adequate parasite load. Moreover, although several helminth species have been shown to modulate immune responses, most in vitro and in vivo studies have focused on the importance of Schistosoma mansoni in down-modulating allergic reactions.

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In vivo alterations in cytokine production following interleukin-12 (IL-12) and anti-IL-4 antibody treatment of CB6F1 mice with chronic cutaneous leishmaniasis

Cited by 19 publications

References 21 publications

Mercury enhances susceptibility to murine leishmaniasis

Mercury enhances susceptibility to murine leishmaniasis

Garlic Induces a Shift in Cytokine Pattern in Leishmania major‐Infected BALB/c Mice

Worms and allergy

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