Granulocyte–colony‐stimulatory factor: a strong inhibitor of natural killer cell function

Schlahsa, Laura; Jaimes, Yarúa; Blasczyk, Rainer; Figueiredo, Constança

doi:10.1111/j.1537-2995.2010.02820.x

Cited by 41 publications

(25 citation statements)

References 38 publications

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“…Scarpellini and Sbracia (2009) did not report on significant side effects of G-CSF application except a mild skin rash and slight leukocyte elevation which corresponds to our data. G-CSF has multiple effects on the immune system like induction of the Th2 answer (Pan et al 1995) and inhibition of NK cells (Schlahsa et al 2011) and blood mononuclear cells (Kitabayashi et al 1995;Sugita et al 2003). Moreover, experiments on animals and cell lines have proven a protective impact on fetuses (Novales et al 1993) and trophoblast cells (Marino and Roguin 2008).…”

Section: Discussionmentioning

confidence: 99%

Granulocyte-Colony Stimulating Factor as Treatment Option in Patients with Recurrent Miscarriage

Santjohanser¹,

Knieper

Franz

et al. 2013

Arch. Immunol. Ther. Exp.

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In 1-5 % of patients during childbearing years recurrent miscarriages (RM) occur. There are established risk factors like anatomical, endocrine and hemostatic disorders as well as immunological changes in the maternal immune system. Nevertheless, further elucidation of the pathogenesis remains a matter of debate. In addition, there are no standardized immunological treatment strategies. Recent studies indicate possible effects of tumor necrosis factor a blocker and granulocyte-colony stimulating factor (G-CSF) concerning live birth rate (LBR) in RM patients. Therefore, we performed a retrospective cohort study in patients undergoing assisted reproductive treatment (ART) with known RM analysing the possible benefits of G-CSF application. From January 2002 to December 2010, 127 patients (199 cylces) with RM (at least 2 early miscarriages) 49 (72 cycles) receiving G-CSF and 78 (127 cycles) controls receiving either no medication (subgroup 1) or Cortisone, intravenous immunoglobulins or low molecular weight heparin (subgroup 2) undergoing ART for in vitro fertilisation/intracytoplasmic sperm injection were analysed. G-CSF was administered weekly once (34 Mill) in 11 patients, 38 patients received 2 9 13 Mill G-CSF per week until the 12th week of gestation. Statistical analysis was performed with SPSS for Windows (19.0), p \ 0.05 significant. The mean age of the study population was 37.3 ± 4.4 years (mean ± standard deviation) and differed not significantly between patients and subgroups. However, the number of early miscarriages was significantly higher in the G-CSF group as compared to the subgroups (G-CSF 2.67 ± 1.27, subgroup 1 0.85 ± 0.91, subgroup 2 0.64 ± 0.74) and RM patients receiving G-CSF had significantly more often a late embryo transfer (day 5) (G-CSF 36.7 %, subgroup 1 12.1 %, subgroup 2 8.9 %). The LBR of patients and the subgroups differed significantly (G-CSF 32 %, subgroup 1 13 %, subgroup 2 14 %). Side effects were present in less than 10 % of patients, consisting of irritation at the injection side, slight leukocytosis, rise of the temperature (\38°C), mild bone pain and hyperemesis gravidarum. None of the newborn showed any kind of malformations. According to our data, G-CSF seems to be a safe and promising immunological treatment option for RM patients. However, with regard to the retrospective setting and the possible bias of a higher rate of late embryo transfers in the G-CSF group additional studies are needed to further strengthen our results.

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Section: Discussionmentioning

confidence: 99%

Granulocyte-Colony Stimulating Factor as Treatment Option in Patients with Recurrent Miscarriage

Santjohanser¹,

Knieper

Franz

et al. 2013

Arch. Immunol. Ther. Exp.

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“…17 Schlahsa et al 18 indicated that the expression of the activating receptors (NKp46 and NKG2D) and inhibitory receptors (KIR2DL1 and KIR2DL2) decreased about 40-64% and 46% (each), respectively, by G-CSF treatment. Moreover, the cell line we used in this study, NK-92MI cells, lacks most of the inhibitory receptors, 19 but the direct inhibitory effect of G-CSF on NK cell activity has a similar response in G-CSFtreated NK-92MI cells (Figure 3a from G-CSF-mobilized stem cell donors of both sexes (Figure 1a).…”

Section: Discussionmentioning

confidence: 99%

G-CSF downregulates natural killer cell-mediated cytotoxicity in donors for hematopoietic SCT

et al. 2011

Bone Marrow Transplant

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“…Several studies have demonstrated that G-CSF mobilizes regulatory T and NK cells into the peripheral blood, impairs T and NK TH1-type reactions and produces an immune-suppressive environment. [33][34][35][36][37][38][39] All patients in our cohort received G-CSF post transplant, starting from day +6 till engraftment. Interestingly our results align with those by Le Blanc et al…”

Section: Discussionmentioning

confidence: 99%

Low blood lymphocyte count at 30 days post transplant predicts worse acute GVHD and survival but not relapse in a large retrospective cohort

Gul

Meter

Abidi

et al. 2015

Bone Marrow Transplant

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Multiple reports have shown that low absolute lymphocyte count at day 30 (ALC30) after allogeneic hematopoietic SCT (AHSCT) is associated with higher risk of disease relapse and worse OS. However, these reports included heterogeneous populations with different grafts and GVHD prophylaxis. Therefore, we retrospectively evaluated the association of ALC30 with transplant outcomes in a cohort of 381 consecutive patients who underwent AHSCT between 2005 and 2010 and received T-replete PBSC grafts and Tacrolimus/Mycophenolate combination as GVHD prophylaxis. Median follow-up was 57 months. Lower ALC30 (⩽400 × 10 6 /L) was associated with lower OS and increased nonrelapse mortality (NRM) for the whole cohort as well as for recipients of SD and UD grafts separately. Lower ALC30 was associated with more severe acute GVHD (aGVHD; III-IV) for the entire cohort as well as for the SD and UD groups. No association was found between lower ALC30 and relapse. Pretransplant factors associated with lower ALC30 were: unrelated donors; HLA mismatch; older donors; lower recipient age; and lower CD34+ cell dose. In this large retrospective study, ALC30 ⩽ 400 × 10 6 /L was associated with worse OS, increased NRM and severe aGVHD.

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Granulocyte–colony‐stimulatory factor: a strong inhibitor of natural killer cell function

Abstract: G-CSF was demonstrated to be a strong inhibitor of NK cells activity and may prevent their graft-versus-leukemia effect after transplantation.

Cited by 41 publications

References 38 publications

Granulocyte-Colony Stimulating Factor as Treatment Option in Patients with Recurrent Miscarriage

Granulocyte-Colony Stimulating Factor as Treatment Option in Patients with Recurrent Miscarriage

G-CSF downregulates natural killer cell-mediated cytotoxicity in donors for hematopoietic SCT

Low blood lymphocyte count at 30 days post transplant predicts worse acute GVHD and survival but not relapse in a large retrospective cohort

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