Antibiotics, cytokine production and cross-talk with cancer cells

Excerpt:


J Pharm Pharmacogn Res 4(4): 134-143, 2016. Original Article | Artículo Original The effect of antibiotics on cytokine production by mononuclear cells and the cross-talk with colon cancer cells [Efecto de antibióticos sobre la producción de citocinas por células mononucleares y la interacción con células de cáncer de colon] Meir Djaldetti1*, Nimrod Nachmias2, Hanna Bessler1 1Laboratory for Immunology and Hematology … Continue reading Antibiotics, cytokine production and cross-talk with cancer cells

J Pharm Pharmacogn Res 4(4): 134-143, 2016.

Original Article | Artículo Original

The effect of antibiotics on cytokine production by mononuclear cells and the cross-talk with colon cancer cells

[Efecto de antibióticos sobre la producción de citocinas por células mononucleares y la interacción con células de cáncer de colon]

Meir Djaldetti1*, Nimrod Nachmias2, Hanna Bessler1

1Laboratory for Immunology and Hematology Research, 2Department of Orthopedics, Rabin Medical Center, Hasharon Hospital, 7, Keren Kayemet St Petah Tiqva, and the Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.

*E-mail: meird@clalit.org.il

Abstract

Context: Antibiotics belong to the powerful weapons applied against microbial infections. It is notable that in addition to their antimicrobial effect they express immunomodulatory and anti-cancer activities.

Aims: To explore the effect of four antibiotics on the immune cross-talk between peripheral blood mononuclear cells (PBMC) and colon carcinoma cells from two human lines.

Methods: Cefotaxime, meropenem, ampicillin and vancomycin were separately added to PBMC co-incubated with cells from two human colon carcinoma cell lines, i.e. HT-29 and RKO. After 24 hours, the level of the following cytokines produced by PBMC was evaluated: IL-6, IL-1ra, IL-1β, TNFα, IFNγ and IL-10.

Results: All four antibiotics did not affect the generation of IL-6 and IL-1ra in both co-cultures. On the other hand all of them restrained the production of IL-1β by PBMC incubated with HT-29 cells. In the same incubation mixture cefotaxime, vancomycin and meropenem decreased IFNγ and IL-10 production, while ampicillin and vancomycin inhibited TNFα. As for PBMC incubated with RKO carcinoma cells, cefotaxime inhibited the production of IL-1β, IFNγ and mildly of IL-10, whereas vancomycin repressed that of IL-1β, TNFα and IFNγ. Notably, vancomycin increased the production of IL-1β and decreased that of TNFα and IFNγ. The results indicate that the four antibiotics examined exert a modulatory effect on the immune cross-talk between PBMC and human colon cancer cells from two lines expressed by a different impact on pro-and anti-inflammatory cytokines generation.

Conclusions: These findings support the conception that antibiotics may express not only an anti-microbial effect, but also possess an anti-cancer activity that may be considered for integration to the therapeutic arsenal against cancer.

Keywords: Ampicillin; cefotaxime; colon carcinoma cells; cytokines; meropenem; mononuclears; vancomycin.

Resumen

Contexto: Los antibióticos son armas poderosas aplicadas contra las infecciones microbianas. Además de su efecto antimicrobiano expresan actividades inmunomoduladoras y contra el cáncer.

Objetivos: Explorar el efecto de cuatro antibióticos sobre la interacción inmune entre las células mononucleares de sangre periférica (PBMC) y células de carcinoma de colon de dos líneas humanas.

Métodos: Cefotaxima, meropenem, ampicilina y vancomicina se añadieron por separado a PBMC co-incubadas con células de dos líneas de carcinoma de colon humano (HT-29 y RKO). Después de 24 horas, se evaluaron las concentraciones de las siguientes citocinas producidas por PBMC: IL-6, IL-1ra, IL-1β, TNFα, IFNγ e IL-10.

Resultados: Los cuatro antibióticos no afectaron la generación de IL-6 e IL-1ra en ambos co-cultivos. Por otra parte, todos contuvieron la producción de IL-1β por PBMC incubadas con células HT-29. En la misma mezcla de incubación cefotaxima, vancomicina y meropenem disminuyeron la producción de IFNγ e IL-10, mientras que la ampicilina y vancomicina inhibieron TNFα. Cuando PBMC se incubaron con células RKO, cefotaxima inhibió la producción de IL-1β, IFNγ y ligeramente de IL-10, mientras que la vancomicina reprimió las de IL-1β, TNFα e IFNγ. En particular, la vancomicina aumentó la producción de IL-1β y disminuyó las de TNFα e IFNγ. Los resultados indican que los cuatro antibióticos examinados ejercieron un efecto modulador sobre la interacción inmune entre PBMC y las células de cáncer de colon humano a partir de dos líneas, expresadas por un impacto diferente sobre la generación de citocinas pro- y anti-inflamatorias.

Conclusiones: Estos hallazgos apoyan la idea de que los antibióticos pueden presentar no sólo un efecto anti-microbiano, también poseen una actividad anti-cancerígena que pudiera ser considerada para la integración de éstos al arsenal terapéutico contra el cáncer.

Palabras Clave: Ampicilina; cefotaxima; células de carcinoma de colon; citocinas; meropenem; mononucleares; vancomicina.

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Citation Format: Meir Djaldetti, Nimrod Nachmias, Hanna Bessler (2016) The effect of antibiotics on cytokine production by mononuclear cells and the cross-talk with colon cancer cells. J Pharm Pharmacogn Res 4(4): 134-143.
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Krishnananthasivam S, Sathkumara HD, Corea E, Natesan M, De Silva AD (2017) Gene expression profile of human cytokines in response to Burkholderia pseudomallei infection. mSphere 2: e00121-17. DOI: 10.1128/mSphere.00121-17

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