Role of iron in T cell activation: Th1 clones differ from TH2 clones in their sensitivity to inhibition of DNA synthesis caused by IGG mabs against the transferrin receptor and the iron chelator deferoxamine

Thorson, John; Smith, Kevin M.; Gómez, Francisco; Naumann, Paul W.; Kemp, John D.

doi:10.1016/0008-8749(91)90336-a

Cited by 88 publications

(55 citation statements)

References 23 publications

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“…Our findings are consistent with previous studies demonstrating that iron overload suppresses cell-mediated immune responses and inflammation, including production of canonical Th1 cytokines such as IFN-γ or IL-12 (29)(30)(31). However, reduction of iron levels with chelators other than deferasirox has also been shown to suppress Th1 polarization and inflammatory responses and to favor Th2 responses (32,33), so the effects of intracellular iron levels and iron chelation on host immune responses appear to be protean.…”

Section: Figuresupporting

confidence: 91%

The iron chelator deferasirox protects mice from mucormycosis through iron starvation

Ibrahim¹,

Gebermariam²,

Fu³

et al. 2007

J. Clin. Invest.

288

274

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Mucormycosis causes mortality in at least 50% of cases despite current first-line therapies. Clinical and animal data indicate that the presence of elevated available serum iron predisposes the host to mucormycosis. Here we demonstrate that deferasirox, an iron chelator recently approved for use in humans by the US FDA, is a highly effective treatment for mucormycosis. Deferasirox effectively chelated iron from Rhizopus oryzae and demonstrated cidal activity in vitro against 28 of 29 clinical isolates of Mucorales at concentrations well below clinically achievable serum levels. When administered to diabetic ketoacidotic or neutropenic mice with mucormycosis, deferasirox significantly improved survival and decreased tissue fungal burden, with an efficacy similar to that of liposomal amphotericin B. Deferasirox treatment also enhanced the host inflammatory response to mucormycosis. Most importantly, deferasirox synergistically improved survival and reduced tissue fungal burden when combined with liposomal amphotericin B. These data support clinical investigation of adjunctive deferasirox therapy to improve the poor outcomes of mucormycosis with current therapy. As iron availability is integral to the pathogenesis of other infections (e.g., tuberculosis, malaria), broader investigation of deferasirox as an antiinfective treatment is warranted.

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Section: Figuresupporting

confidence: 91%

The iron chelator deferasirox protects mice from mucormycosis through iron starvation

Ibrahim¹,

Gebermariam²,

Fu³

et al. 2007

J. Clin. Invest.

288

274

View full text Add to dashboard Cite

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“…We have discovered the hydrazino anthrinilate compound 1, which shows a good inhibition of Th1 cytokines but only a partial effect 29,30 Th1 cells, either developing or terminally differentiated, are known to have a labile pool of iron that is required for their proper functions. 31 From the microarray analysis, we observed that multiple IL-12/IL-18 inducible genes, many of which control the basic functions of the cells, were affected by iron chelation. It is difficult to isolate 1 particular mechanism that contributes the most to the inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…2A). 31 We first compared compound 1, NIH, and DFO in the IL-12/IL-18-mediated IFN-γ release assay. Compound 1 and NIH demonstrated similar IC 50 s (around 200 nM), whereas DFO was about 15-to 20-fold weaker (Fig.…”

Section: Comparison Of the Hydrazino Anthranitlate Iron Chelator Compmentioning

confidence: 99%

Identifying Modulators of hERG Channel Activity Using the PatchXpress® Planar Patch Clamp

Leung¹,

Holbrook²,

King³

et al. 2005

SLAS Discovery

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“…However, B-cells may have larger iron storage pools than T-cells and may be more resistant to iron-limiting conditions, for example in the presence of antitransferrin receptor antibody plus the iron chelator desferrioxamine . Among T-cells, T-helper (Th)l cells are much more sensitive than Th2 clones to the intracellular iron depletion produced by the combination of antitransferrin receptor antibody plus desferrioxamine (Thorson et al, 1991). Human peripheral blood mononuclear cells still respond to phytohemagglutinin (PHA) in iron-depleted medium , and it is necessary to chelate intracellular iron with desferrioxamine to block this , providing further evidence of iron stores and efficient uptake systems in activated lymphocytes.…”

Section: Effects Of Iron Deficiency On Immune Functionmentioning

confidence: 99%

Military Strategies for Sustainment of Nutrition and Immune Function in the Field

Poos¹,

Costello²,

Carlson-Newberry³

1999

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The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.Cover: Resting monocyte/macrophage being activated to produce proinflammatory cytokines which form complexes with receptor binding proteins. Adapted from COMMITTEE ON MILITARY NUTRITION RESEARCHROBERT O. NESHEIM (Chair, through June 30, 1998) (FNB), Institute of Medicine, National Academy of Sciences. Other workshops or symposia have included such topics as food components to enhance performance; nutritional needs in hot, cold, and high-altitude environments; body composition and physical performance; nutrition and physical performance; cognitive testing methodology; and fluid replacement and heat stress. These workshops form part of the response that the CMNR provides to the Commander, U. HISTORY OF THE COMMITTEEThe CMNR was established in October 1982 following a request by the Assistant Surgeon General of the Army that the Board on Military Supplies of the National Academy of Sciences set up a special committee. The purpose of this committee was to advise the U.S. Department of Defense on the need for and conduct of nutrition research and related issues. The CMNR was transferred to the FNB in 1983. The CMNR's current tasks are• to identify nutritional factors that may critically influence the physical and mental performance of military personnel under all environmental extremes,• to identify deficiencies in the existing database, • to recommend research that would remedy these deficiencies as well as approaches for studying the relationship of diet to physical and mental performance, and• to review and advise on standards for military feeding systems.Within this context, the CMNR was asked to focus on nutrient requirements for performance during operational missions rather than requirements for military personnel in garrison (the latter were judged to be not significantly different from those of the civilian population).Although the membership of the committee has changed periodically, the disciplines represented consistently have included human nutrition, nutritional biochemistry, performance physiology, food science, and psychology. For issues that require broader expertise than exists within the committee, the CMNR has convened workshops or utilized consultants. The workshops provide additional state-of-the-art scientific information and informed opinion for the consideration of the committee. COMMITTEE TASKS AND PROCEDURESThe request for this review of nutrition and immune function and its application to military operations originated with Army scientists from USARIEM and USAMRMC. In December 1995, a committee subgroup of the CMNR participated in a series of conference calls with USARIEM, USAMRMC, and other CMNR members to identify the key areas that should be reviewed and to solicit suggestions for names...

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Role of iron in T cell activation: Th1 clones differ from TH2 clones in their sensitivity to inhibition of DNA synthesis caused by IGG mabs against the transferrin receptor and the iron chelator deferoxamine

Cited by 88 publications

References 23 publications

The iron chelator deferasirox protects mice from mucormycosis through iron starvation

The iron chelator deferasirox protects mice from mucormycosis through iron starvation

Identifying Modulators of hERG Channel Activity Using the PatchXpress® Planar Patch Clamp

Military Strategies for Sustainment of Nutrition and Immune Function in the Field

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