visceral leishmania inoculation

[Rick Kenney]

Milena -

Hank Murray believes they found the magic a few years ago:

Murray HW, Hariprashad J, Coffman RL. Behavior of visceral Leishmania
donovani in an experimentally induced T helper cell 2 (Th2)-associated
response model. J Exp Med 1997;185:867-74.

Although implicated in the clinical expression of human visceral
leishmaniasis, a disease-exacerbating T helper cell 2 (Th2)-associated
immune response involving interleukin-4 (IL-4) and/ or IL-10 is not readily
detectable in experimental visceral infection. To overcome this obstacle to
analyzing visceral Leishmania donovani in this relevant immunopathogenetic
environment, we sought a model in which a Th2 response induces noncuring
infection. Four initial approaches were tested primarily in BALB/c mice
which control intracellular L. donovani via an IL-12- and interferon-gamma
(IFN-gamma)-dependent Th1 mechanism: (a) modifying the cytokine milieu when
the parasite is first encountered (treatment with exogenous IL-4 or
anti-IL-12), (b) providing sustained endogenous exposure to a Th2 cytokine
(infection of IL-4 transgenic mice), (c) increasing the parasite challenge
inoculum, and (d) injecting heat-killed L. major promastigotes (HKLMP) to
induce a cross-reactive Th2 response to live L. donovani. Only the last
approach generated a functional Th2-type response that induced disease
exacerbation accompanied by inhibition of tissue granuloma assembly. In
HKLMP-primed BALB/c mice, prophylaxis with anti-IL-4, anti-IL-10, or
exogenous IL-12 (but not IFN-gamma) readily restored resistance. In primed
mice with established visceral infection, treatment with either IL-12 or
IFN-gamma also successfully induced antileishmanial activity. The results
in this model (a) suggest that rather than acting alone, IL- 4 and IL-10
may act in concert to prevent acquisition of resistance to L. donovani, (b)
reemphasize the capacity of IL-12 to reverse early Th2- related effects,
and (c) demonstrate that Th1 cytokines (IL-12, IFN- gamma) have therapeutic
action in an established systemic infection despite the presence of a
disease-exacerbating Th2-type response.

Good luck with your experiments!

Rick Kenney

>Dear colleagues,
>
>according to the literature, the way of L.donovani/L.infantum inoculation
>is i.v. or i.c. I think this mode is even more artificial than infecting
>with L.major (s.c.) Does anybody know about succesfull subcutaneous
>infection with L.infantum/L.donovani, which would result in visceral disease?
>
>Thank you in advance for your answers
>Milena
>Milena Svobodova
>Dept Biochemistry
>Univ of Kentucky Medical Center
>800 Rose St
>Lexington KY 40536-0298 USA
>tel (606) 323-5042
>fax (606) 323-1037


--------------------------------------------------------------------------
Rick Kenney - leishmaniac            For two personalities to meet is like
FDA/CBER/OVRR/DAPP/LPBB                    mixing two chemical substances:
NIH Bldg 29, Rm 429, HFM-416           If there is any combination at all,
1401 Rockville Pike                                  both are transformed.
Rockville, MD 20852-1448
(301) 496-4776 (lab), 480-5527 (fax)                            C.G. Jung
email: kenney at cber.fda.gov or rkenney at helix.nih.gov
--------------------------------------------------------------------------