Iron chelating agents, which permeate through erythrocytic and parasite membranes, are effective against Plasmodium falciparum in vitro. However, the protective effect in humans is transient. We examined the antiplasmodial capacity of several iron chelators in vitro and in vivo. The chelators 3/3hb/2m and 3/2hb/b (together, MoB) were more effective against P. falciparum in vitro than desferrioxamine (DFO) and Salicylaldehyde isonicotinoyl hydrazone (SIH) (together, DoS). Despite similar pharmacokinetics of all iron chelators, mice infected with Plasmodium vinckei and treated with MoB succumbed to malaria, whereas DoS-treated mice survived. However, even in the surviving mice, peak parasitemias were above 30%. These results indicate that the direct effects of the drugs on the parasites were not responsible alone for the complete recovery of the mice. We suggest that the recovery is related to differential effects of the drugs on various immune functions. We concentrated on the effect of the iron chelators on B cell and T cell proliferation and on allogeneic stimulation (MLR), interleukin-10 (IL-10), γ-interferon (γ-IFN), tumor necrosis factor-α (TNF-α), and radical production. All the iron chelators examined inhibited the in vitro proliferation of B cells and T cells, and MLR. This may explain why iron chelators are only slightly efficient in treating human malaria. However, the inhibitory effects of MoB on B cell and T cell proliferation and on MLR were more pronounced than those of DoS. In addition, the release of free radicals by effector cells was inhibited to a greater extent by MoB than by DoS. These results may explain why MoB, which was more efficient in vitro, was not effective in vivo. The DoS effects on the in vitro secretion of cytokines correlate with their in vivo effect; there was a decrease of IL-10 and a parallel increase in γ-IFN and TNF-α production by human mononuclear cells. MoB, which could not rescue the animals from malaria, did not affect IL-10 and TNF-α, but reduced γ-IFN levels. Identical results were obtained when using monocytes instead of mononuclear cells (except for γ-IFN, which is not produced by monocytes). Our results indicate that an iron chelator, or any antiparasitic drug that kills the parasites in vitro, should also be selected for further evaluation on the basis of its reaction with immune components; it should not interfere with crucial protective immunological processes, but it may still alleviate parasitemia by positive immune modulation.
Skip Nav Destination
Article navigation
February 2006
Research Article|
February 01 2006
IRON CHELATORS: CORRELATION BETWEEN EFFECTS ON PLASMODIUM SPP. AND IMMUNE FUNCTIONS
Jacob Golenser;
Jacob Golenser
Department of Parasitology—The Kuvin Center for the Research of Infectious and Tropical Diseases, The Hebrew University of Jerusalem, Jerusalem, Israel. [email protected]
Search for other works by this author on:
Abraham Domb;
Abraham Domb
Department of Parasitology—The Kuvin Center for the Research of Infectious and Tropical Diseases, The Hebrew University of Jerusalem, Jerusalem, Israel. [email protected]
* Department of Medicinal Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel
Search for other works by this author on:
Talya Mordechai-Daniel;
Talya Mordechai-Daniel
Department of Parasitology—The Kuvin Center for the Research of Infectious and Tropical Diseases, The Hebrew University of Jerusalem, Jerusalem, Israel. [email protected]
* Department of Medicinal Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel
Search for other works by this author on:
Benny Leshem;
Benny Leshem
Department of Parasitology—The Kuvin Center for the Research of Infectious and Tropical Diseases, The Hebrew University of Jerusalem, Jerusalem, Israel. [email protected]
† Ministry of Health, Chief Scientist Office, Jerusalem, Israel
Search for other works by this author on:
Adrian Luty;
Adrian Luty
Department of Parasitology—The Kuvin Center for the Research of Infectious and Tropical Diseases, The Hebrew University of Jerusalem, Jerusalem, Israel. [email protected]
‡ Human Parasitology Department, The Institute of Tropical Medicine, Tuebingen, Germany
Search for other works by this author on:
Peter Kremsner
Peter Kremsner
Department of Parasitology—The Kuvin Center for the Research of Infectious and Tropical Diseases, The Hebrew University of Jerusalem, Jerusalem, Israel. [email protected]
‡ Human Parasitology Department, The Institute of Tropical Medicine, Tuebingen, Germany
Search for other works by this author on:
J Parasitol (2006) 92 (1): 170–177.
Citation
Jacob Golenser, Abraham Domb, Talya Mordechai-Daniel, Benny Leshem, Adrian Luty, Peter Kremsner; IRON CHELATORS: CORRELATION BETWEEN EFFECTS ON PLASMODIUM SPP. AND IMMUNE FUNCTIONS. J Parasitol 1 February 2006; 92 (1): 170–177. doi: https://doi.org/10.1645/GE-3517.1
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionCiting articles via
MOLECULAR AND NEW MORPHOLOGICAL DATA ON NEMATODE HEDRURIS DRATINI FOUND PARASITIZING PSEUDIS MINUTA (ANURA: HYLIDAE)
Martin M. Montes, Yasmin Croci, Jorge Barneche, Dario Balcazar, German F. Reig Cardarella, Sergio R. Martorelli
CLITELLATE (ANNELIDA: CLITELLATA) PARASITES AND PREDATORS OF NORTH AMERICAN HERPETOFAUNA: CHECKLIST OF SPECIES, IDENTIFICATION KEY, AND A NEW RECORD FOR MEXICO
Manuel De Luna, Roberto García-Barrios, Diane P. Barton, Leonardo García-Vázquez
LOUSY ASSOCIATIONS: SUCKING LICE (PHTHIRAPTERA: ANOPLURA) PARASITIZING RODENTS AND LAGOMORPHS IN THE DESERT NATIONAL WILDLIFE REFUGE, NEVADA
Sara B. Weinstein, John P. Dumbacher, Lance A. Durden
A NEW SPECIES OF ACANTHOBOTHRIUM (CESTODA: ONCHOPROTEOCEPHALIDEA), PARASITE OF THE GIANT ELECTRIC RAY NARCINE ENTEMEDOR JORDAN AND STARKS, 1895 (BATOIDEA: TORPEDINIFORMES) FROM MEXICO
Erick Rodríguez-Ibarra, Berenice Adán-Torres, Fernando Ruiz-Escobar, Gerardo Torres-Carrera
SEROPREVALENCE OF TOXOPLASMA GONDII IN GOATS FROM SOUTHWESTERN MISSISSIPPI, USA
Alexander D. W. Acholonu, Jamela S. Alexander