J Vet Sci.  2018 Sep;19(5):708-715. 10.4142/jvs.2018.19.5.708.

Bee venom stimulation of a lung meridian acupoint reduces inflammation in carrageenan-induced pleurisy: an alternative therapeutic approach for respiratory inflammation

• Choi HS
• Kang SY
• Roh DH
• Choi SR
• Ryu Y
• Lee JH

• KMID: 2420941
• DOI: http://doi.org/10.4142/jvs.2018.19.5.708

Abstract

Respiratory inflammation is a frequent and fatal pathologic state encountered in veterinary medicine. Although diluted bee venom (dBV) has potent anti-inflammatory effects, the clinical use of dBV is limited to several chronic inflammatory diseases. The present study was designed to propose an acupoint dBV treatment as a novel therapeutic strategy for respiratory inflammatory disease. Experimental pleurisy was induced by injection of carrageenan into the left pleural space in mouse. The dBV was injected into a specific lung meridian acupoint (LU-5) or into an arbitrary non-acupoint located near the midline of the back in mouse. The inflammatory responses were evaluated by analyzing inflammatory indicators in pleural exudate. The dBV injection into the LU-5 acupoint significantly suppressed the carrageenan-induced increase of pleural exudate volume, leukocyte accumulation, and myeloperoxidase activity. Moreover, dBV acupoint treatment effectively inhibited the production of interleukin 1 beta, but not tumor necrosis factor alpha in the pleural exudate. On the other hand, dBV treatment at non-acupoint did not inhibit the inflammatory responses in carrageenan-induced pleurisy. The present results demonstrate that dBV stimulation in the LU-5 lung meridian acupoint can produce significant anti-inflammatory effects on carrageenan-induced pleurisy suggesting that dBV acupuncture may be a promising alternative medicine therapy for respiratory inflammatory diseases.

Keyword

acupuncture; anti-inflammation; bee venoms; carrageenan-induced pleurisy

MeSH Terms

Acupuncture
Acupuncture Points*
Animals
Bee Venoms*
Bees*
Carrageenan
Complementary Therapies
Exudates and Transudates
Hand
Inflammation*
Interleukin-1beta
Leukocytes
Lung*
Mice
Peroxidase
Pleurisy*
Tumor Necrosis Factor-alpha
Veterinary Medicine
Bee Venoms
Carrageenan
Interleukin-1beta
Peroxidase
Tumor Necrosis Factor-alpha

Figure

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  Fig. 1 Graphs illustrating the effect of diluted bee venom (dBV) treatment on exudate volume in carrageenan (CA)-induced pleurisy. Intrapleural injection of CA significantly increased the exudate volume compared to that of sham animals (Sham). The 0.8 mg/kg dBV apipuncture of LU-5 (CA + BV-A 0.8) significantly blocked the increase of exudate volume compared to that of vehicle-treated CA mouse (CA + Veh) (p < 0.05). However, 0.08 mg/kg dBV apipuncture of LU-5 (CA + BV-A 0.08) or 0.8 mg/kg dBV apipuncture of non-acupoint (CA + BV-NA 0.8) did not change the exudate volume compared to that of vehicle-treated CA mouse (CA + Veh). ***p < 0.001 compared to that of sham animals.

• 

  Fig. 2 Graphs illustrating the effect of diluted bee venom (dBV) treatment on leukocyte accumulation in pleural exudate. Intrapleural injection of carrageenan (CA) markedly induced the accumulation of leukocytes into the CA-injected pleural cavity compared to that of sham animals (Sham). The 0.8 mg/kg dBV apipuncture of LU-5 (CA + BV-A 0.8) significantly inhibited the accumulation of leukocytes in pleural exudate compared with that of vehicle-treated CA mouse (CA + Veh) (p < 0.01). However, 0.08 mg/kg dBV apipuncture of LU-5 (CA + BV-A 0.08) or 0.8 mg/kg dBV apipuncture of non-acupoint (CA + BV-NA 0.8) did not affect the number of leukocytes in pleural exudate compared to that of vehicle-treated CA group (CA + Veh). ***p < 0.001 compared to that of sham animals.

• 

  Fig. 3 Graphs illustrating the effect of diluted bee venom (dBV) treatment on myeloperoxidase (MPO) activity in pleural exudate. Intrapleural injection of carrageenan (CA) significantly increased the MPO activity in pleural exudate compared to that of sham animals (Sham). The CA mouse treated with 0.8 mg/kg dBV apipuncture of LU-5 (CA + BV-A 0.8) had significantly reduced MPO activity as compared to that of vehicle-treated CA mouse (CA + Veh) (p < 0.05). However, the CA mouse treated with 0.08 mg/kg dBV apipuncture of LU-5 (CA + BV-A 0.08) or 0.8 mg/kg dBV apipuncture of non-acupoint (CA + BV-NA 0.8) did not show significant changes in MPO activity compared to that of vehicle-treated CA mouse (CA + Veh). RFU, relative fluorescence units. ***p < 0.001 compared to that of sham animals.

• 

  Fig. 4 Graphs illustrating the effect of diluted bee venom (dBV) treatment on levels of proinflammatory cytokines in pleural exudate. Intrapleural injection of carrageenan (CA) significantly increased the production of interleukin 1 beta (IL-1β) (A) and tumor necrosis factor alpha (TNF-α) (B) in pleural exudate compared to that of sham animals (Sham). (A) 0.8 mg/kg dBV apipuncture of LU-5 (CA + BV-A 0.8) significantly inhibited the upregulation of IL-1β production compared to that of vehicle-treated CA mouse (CA + Veh) (p < 0.05). However, 0.08 mg/kg dBV apipuncture of LU-5 (CA + BV-A 0.08) or 0.8 mg/kg dBV apipuncture of non-acupoint (CA + BV-NA 0.8) did not affect the level of IL-1β. (B) Treatment of dBV on neither the LU-5 acupoint nor a non-acupoint did not change the level of TNF-α compared to that of vehicle-treated CA mouse (CA + Veh). ***p < 0.001 compared to that of sham animals.

• 

  Fig. 5 Graphs and photomicrographs illustrating the effect of diluted bee venom (dBV) treatment on Fos expression in the ipsilateral (Ipsi) and contralateral (Contra) hypothalamic paraventricular nucleus (PVN). (A) Two hours after 0.8 mg/kg dBV stimulation of the LU-5 acupoint, the number of Fos-immunoreactive (Fos-ir) neurons significantly increased in the contralateral side of PVN in the dBV-treated group (BV-A 0.8) compared to that of the vehicle-treated group (Veh-A) (p < 0.05). (B) Representative PVN sections demonstrating the typical pattern of Fos-ir in the groups. Scale bars = 100 µm.

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