Thalidomide enhances both primary and secondary host resistances to infection by a neutrophil-related mechanism in female B6C3F1 mice

Guo, Tai L.; P., Rui; Karrow, Niel A.; Zhang, Ling X.; Pruett, Stephen B.; Germolec, Dori R.; White, Kimber L.

doi:10.1016/j.taap.2005.04.014

Cited by 5 publications

(8 citation statements)

References 36 publications

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“…Furthermore, these neutrophils were functional as indicated by an increased MPO activity in the spleen and bone marrow following Thd treatment, as well as our previous reports that Thd-mediated enhancement in neutrophil responses was responsible for the increased host resistance against both primary and secondary Listeria monocytogenes infection (Karrow et al, 2003;Guo et al, 2005). Taken together, we can conclude that Thd enhancement of neutrophil function is one of the mechanisms of action that is responsible for Thd's immunomodulatory efficacy in a variety of diseases, which may be particularly true for MDS.…”

Section: Discussionsupporting

confidence: 69%

“…In our previous studies, we have provided evidence that Thd treatment enhanced host resistance to both primary and secondary L. monocytogenes infections by a neutrophil-related mechanism in female B6C3F1 mice (Guo et al, 2005). Neutrophil numbers in the spleen and liver were increased in Thd-treated and L. monocytogenes-infected mice.…”

Section: Introductionmentioning

confidence: 88%

“…with Thd for 14 or 28 days. One dose of Thd (100 mg/kg) was used in this study since our previous studies have demonstrated that Thd at 100 mg/kg was an optimal dose for modulating the immune responses and host resistances (Karrow et al, 2003;Guo et al, 2005). Additionally, this amount of Thd in mice is equivalent to a clinical human treatment dose (approximately 400 mg/day) in terms of milligram per square meter of body surface (Marriott et al, 1999), which usually gives more accurate interspecies extrapolation (Hodgson, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…Our previous reports have shown that treatment with Thd at 30-150 mg/ kg (i.p.) for either 14 or 28 days could increase host resistance to L. monocytogenes infection by modulating neutrophil function (Karrow et al, 2003;Guo et al, 2005). Therefore, both the 14-day and 28-day treatment regimens were employed in this study to further determine how Thd treatment increased neutrophil responses.…”

Section: Introductionmentioning

confidence: 99%

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Differential surface expression of CD18 and CD44 by neutrophils in bone marrow and spleen contributed to the neutrophilia in thalidomide-treated female B6C3F1 mice

Auttachoat¹,

Zheng²,

P.³

et al. 2007

Toxicology and Applied Pharmacology

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Previously, we have reported that thalidomide (Thd) can enhance neutrophil function in female B6C3F1 mice. The present study was intended to evaluate the mechanisms underlying the enhanced neutrophil responses following Thd treatment intraperitoneally (100 mg/kg) for 14 or 28 days. Treatment with Thd increased the numbers of neutrophils in the spleen, peripheral blood, bone marrow, peritoneal cavity and lung of female B6C3F1 mice when compared to the vehicle control mice. Thd treatment for 14 days increased the percentages and the number of neutrophils in the spleen in the first eight hours (peaking at 2 h) after the last Thd treatment, and it returned to the baseline after 24 h. However, Thd treatment for 28 days increased the percentages and number of neutrophils in the spleen even at the 24-h time point after the last Thd treatment. These neutrophils were demonstrated to be functional by the myeloperoxidase activity assay. Further studies have ruled out the possibility of an increased bone marrow granulopoiesis following Thd treatment. Flow cytometric analysis of the surface expression of adhesion molecules suggested that Thd treatment for either 14 or 28 days decreased the surface expression of either CD18 or CD44 by bone marrow neutrophils. On the other hand, the surface expression of both CD18 and CD44 by splenic neutrophils was increased following Thd treatment for 28 days but not for 14 days. No effect was produced for other cell surface molecules such as CD62L and CD11a. It was possible that decreased surface expressions of CD18 and CD44 facilitated neutrophils' release from the bone marrow; increased surface expressions of CD44 and CD18 by splenic neutrophils after 28 days of Thd treatment increased their ability to remain in the periphery. Taken together, Thd treatment increased neutrophils in female B6C3F1 mice, at least partially, through differentially modulating the surface expression of CD18 and CD44 by the neutrophils in the bone marrow and spleen.

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential surface expression of CD18 and CD44 by neutrophils in bone marrow and spleen contributed to the neutrophilia in thalidomide-treated female B6C3F1 mice

Auttachoat¹,

Zheng²,

P.³

et al. 2007

Toxicology and Applied Pharmacology

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“…Increased host resistance to Listeria infection was further supported by the observation that CLT treatment increased the number of neutrophils (Gr-1 + Mac-3 − ) in the spleen (Fig. 4c) because neutrophils are one of the important effector cells to eliminate the bacteria (Guo et al 2005). In the B16F10 melanoma model, no differences in lung tumor nodule formation were observed when compared to vehicle control animals following 28 days CLT treatment (data not shown).…”

Section: Resultsmentioning

confidence: 62%

Immunomodulation in female B6C3F1 mice following treatment with Chai-Ling-Tang, a formula consisting of twelve herbs

Guo

et al. 2011

Orient Pharm Exp Med

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Chai-Ling-Tang (CLT) is a traditional Chinese herbal decoction consisting of twelve different herbs, and it has been used to treat a number of immune related disorders. However, the mechanism for its clinical effectiveness was not fully understood. In this study, CLT's effect on the immune system of female B6C3F1 mice was evaluated by examining the IgM antibody forming cell (AFC) response; natural killer (NK) cell activity; the expression of splenocyte surface markers; concanavalin (Con) A and anti-CD3 antibody-mediated T-lymphocyte proliferation; lipopolysaccharide-mediated-B cell proliferation, and the host resistances to the Listeria monocytogenes bacterial infection and B16F10 melanoma. The results from these studies suggest that the administration of CLT at doses between 400 and 800 mg/kg/day by gavage for 28 days modulates the immune response in female B6C3F1 mice by increasing the number, percentage, and activity of NK cells, both Con A and anti-CD3 antibody-mediated T-cell proliferation, the number of neutrophils, and the host resistance to L. monocytogenes infection. On the other hand, B cell activity was decreased at the 800 mg/kg dose level. In conclusion, CLT produced an enhancement of host resistance to Listeria monocytogenes infection possibly through modulating the function of neutrophils, T cells and NK cells in female B6C3F1 mice using a T regulatory cell-related mechanism.

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Methods to Assess Immunotoxicity*

Guo

White

2010

Comprehensive Toxicology

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Thalidomide enhances both primary and secondary host resistances to infection by a neutrophil-related mechanism in female B6C3F1 mice

Cited by 5 publications

References 36 publications

Differential surface expression of CD18 and CD44 by neutrophils in bone marrow and spleen contributed to the neutrophilia in thalidomide-treated female B6C3F1 mice

Differential surface expression of CD18 and CD44 by neutrophils in bone marrow and spleen contributed to the neutrophilia in thalidomide-treated female B6C3F1 mice

Immunomodulation in female B6C3F1 mice following treatment with Chai-Ling-Tang, a formula consisting of twelve herbs

Methods to Assess Immunotoxicity*

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